Patients &
trained Companions

Medical Professionals


Fibromyalgia (FM) and
Chronic Myofascial Pain & Dysfunction (CMPD)
For Medical Professionals
annotated by Devin J. Starlanyl



References for Research Purposes

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Labat JJ, Guerineau M, Delavierre D et al. 2010. [Symptomatic approach to musculoskeletal dysfunction and chronic pelvic and perineal pain.] Prog Urol 20(12):982-989. [French] "Musculoskeletal pain is certainly underestimated in the management of chronic pelvic and perineal pain."

Lacagnina MJ, Heijnen CJ, Watkins LR, et al. 2021. Autoimmune regulation of chronic pain. Pain Rep. Mar 9;6(1):e905. eCollection. "In this review, we discuss how neuroimmune signaling can contribute to peripheral and central sensitization and promote chronic pain through various autoimmune mechanisms. Using examples primarily from rheumatoid arthritis, complex regional pain syndrome, and channelopathies from potassium channel complex autoimmunity, we suggest that autoantibody signaling at the central nervous system has therapeutic implications for designing novel disease-modifying treatments for chronic pain."

Lacasse A, Bourgault P, Choiniere M. 2016. Fibromyalgia-related costs and loss of productivity: a substantial societal burden. BMC Musculoskelet Disord. 17(1):168. "FMS is associated with a substantial socioeconomic burden. Further research is clearly needed to improve the management of this type of disorder and make better decisions regarding resource allocation." Free PMC Article

Lachaine J, Beauchemin C, Landry PA. 2010. Clinical and economic characteristics of patients with fibromyalgia syndrome. Clin J Pain. 26(4):284-290. “Results of this analysis of the RAMQ (Quebec provincial health plans) database illustrate the high prevalence of comorbidities among patients with a diagnosis of FMS and strongly indicate that the economic burden of FMS is substantial.” [It is vital to discover the initiating cause of the central sensitization of FM, and even more, the comorbidities and other factors that are maintaining it. DJS]

Lago-Rizzardi CD, de Siqueira JT, de Siqueira SR. 2013. Spirituality of chronic orofacial pain patients: Case-control study. J Relig Health. [Aug 29 Epub ahead of print]. This study was from the Neurology Department, University of Sao Paulo Brazil Medical School. "The objective of this study was to investigate spirituality and blood parameters associated with stress in patients with facial musculoskeletal pain. Twenty-four women with chronic facial musculoskeletal pain (CFMP) and 24 healthy women were evaluated with a protocol for orofacial characteristics, research diagnostic criteria for temporomandibular disorders and the Spiritual Perspective Scale. Blood samples were collected to analyze blood count, cortisol, ACTH, C3, C4, thyroid hormones, total immunoglobulin, C-reactive protein and rheumatoid factor. The study group was more spiritualized than control group. Individuals with a high score of spirituality had less myofascial pain, less bruxism and fewer complaints. They also had lower levels of ACTH and IgE. Spirituality was higher in the study group and can be considered an important tool for coping with CFMP".

Lai HH, Gardner V, Ness TJ et al. 2013. Segmental Hyperalgesia to Mechanical Stimulus in Interstitial Cystitis/Bladder Pain Syndrome - Evidence of Central Sensitization. J Urol. [Dec 5 Epub ahead of print.] "Female subjects with IC/BPS showed segmental hyperalgesia to mechanical pressure stimulation in the suprapubic area (T10-T12). This segmental hyperalgesia may be explained in part by spinal central sensitization."

Lai HM, Liu MSY, Lin TJ et al. 2017. Higher DHEAS levels associated with long-term practicing of tai chi. Chin J Physiol. 60(2):124-130. "Tai Chi has many benefits for middle-aged/older individuals including improvements to muscle strength and various body lipid components. DHEAS and testosterone have anti-obesity/anti-aging characteristics and also improve libido, vitality and immunity levels…. the Tai Chi practitioners had higher levels of DHEAS … and lower levels of cortisol….. Thus, Tai Chi practitioners have a higher ratio of DHEAS to cortisol, which might have potential benefits in terms of improving an individual's health-related quality of life during the aging."

Lai PC, Yen CM, Lin MC, et al. Electroacupuncture attenuates fibromyalgia pain via Toll-like Receptor 4 in the mouse brain. Life (Basel). 2023 May 11;13(5):1160. "These mechanisms provide evidence that the analgesic effect of EA is related to the TLR4 pathway. In addition, we showed that inflammation can activate the TLR4 pathway and provided new possible therapeutic targets for FM pain."

Lambova S, Muller-Ladner U. 2017. Capillaroscopic findings in primary fibromyalgia. Curr Rheumatol Rev. [Jun 7 Epub ahead of print] "Although Raynaud's phenomenon (RP) is observed in a significant proportion of patients with primary fibromyalgia, the available data on capillaroscopic findings in primary fibromyalgia are scarce….In our study, the most frequent capillaroscopic finding in patients with primary fibromyalgia was presence of dilated capillaries analogous to primary RP. Capillaroscopic signs suggestive of connective tissue disease could not be found in primary fibromyalgia patients."

Lamotte M, Maugars Y, Le Lay K. 2010. Health economic evaluation of outpatient management of fibromyalgia patients and the costs avoided by diagnosing fibromyalgia in France. Clin Exp Rheumatol. 28(6 Suppl 63):S64-70. "…in France, early diagnosis of fibromyalgia leads to a decrease in resource use and health care costs."

Lamvu G, Carrillo J, Witzeman K et al. 2018. Musculoskeletal considerations in female patients with chronic pelvic pain. Semin Reprod Med. 36(2):107-115. "Persistent pelvic pain conditions are common and affect nearly 25% of the female U.S. population. In a sizable proportion of pelvic pain patients, the pain is caused by musculoskeletal dysfunction; yet, healthcare providers do not routinely evaluate patients for musculoskeletal etiologies. This article provides an overview of the pathophysiology of persistent pelvic pain, as it relates to musculoskeletal disorders. The symptomatology, anatomy, evaluation, and treatment of these disorders are summarized specifically for healthcare providers (including gynecologists) who do not have pelvic musculoskeletal expertise." [The medical establishment must ask itself why these care providers lack such expertise, and how this can be remedied as soon as possible. DJS]

Lan CC, Tseng CH, Chen JH et al. 2016. Increased risk of a suicide event in patients with primary fibromyalgia and in fibromyalgia patients with concomitant comorbidities: A nationwide population-based cohort study. Medicine (Baltimore). 95(44):e5187. "… (W)e found that fibromyalgia patients without comorbidity had an independent but mild risk of a suicide event with adjusted HRs ranging from 1.33 to 1.69 relative to subjects with neither fibromyalgia nor comorbidity. Meanwhile, fibromyalgia patients with comorbidity led to a markedly enhanced risk of a suicide event relative to the matched reference subjects, with adjusted HRs ranging from 1.51 to 8.23. Our analysis confirmed a mild-to-moderate risk of a suicide event in patients with primary fibromyalgia. Attention should be paid to the prevention of suicide in fibromyalgia patients with concomitant comorbidities." Free Article [Fibromyalgia must be taken seriously, and patients given the support they require. Multiple co-existing conditions can provoke amplified symptoms, including pain, and this must be taken into consideration when caring for these patients. DJS]

Landgraf MN, Biebl JT, Langhagen T et al. 2018. Children with migraine: Provocation of headache via pressure to myofascial trigger points in the trapezius muscle? - A prospective controlled observational study. Eur J Pain. 22(2):385-392. "We found an association between trapezius muscle myofascial trigger points and migraine, which might underline the concept of the trigemino-cervical complex, especially in adolescents…. In children with migraine headache can often be induced by pressure to myofascial trigger points, but not by pressure to non-trigger points in the trapezius muscle. This supports the hypothesis of a trigemino-cervical-complex in the pathophysiology of migraine, which might have implications for innovative therapies in children with migraine."

Landmann G, Stockinger L, Gerber B ,et al. Local hyperexcitability of C-nociceptors may predict responsiveness to topical lidocaine in neuropathic pain. PLoS One. 2022 Jul 14;17(7):e0271327. Lidocaine patches reduced spontaneous pain by >1-point NRS in 8 of 28 patients…. Patients with increased pain to 2.5 sec sinusoidal stimulation at 0.2 and 0.4 mA intensity had significantly stronger analgesic effects of lidocaine and in reverse, patients with a pain reduction of >1 NRS had significantly higher pain ratings to continuous 1 min supra-threshold sinusoidal stimulation. In the assessed control skin areas of the patients, enhanced pain upon 1 min 4 Hz stimulation correlated to increased depression scores (HADS). Electrically assessed C-nociceptor excitability identified by slowly depolarizing electrical stimuli might reflect the source of neuropathic pain in some patients and can be useful for patient stratification to predict potential success of topical analgesics. Central neuronal circuitry assessment reflected by increased pain in control skin associated with higher HADS scores suggest central sensitization phenomena in a sub-population of neuropathic pain patients."

Lane E, Clewley D, Koppenhaver S. 2017. Complaints of upper extremity numbness and tingling relieved with dry needling of the teres minor and infraspinatus: A Case Report. J Orthop Sports Phys Ther. 3:1-21."The patient was a 60-year-old female with primary complaints of right shoulder pain and secondary complaints of neck pain and right upper extremity numbness. Cervical spine neurological examination was unremarkable, and manual examination did not reproduce the patient's arm numbness or tingling symptoms. Compression of a trigger point in infraspinatus and teres minor reproduced the patient's primary complaints of shoulder pain. The initial intervention included dry needling (DN), which reproduced her upper extremity numbness. Subsequent treatment included manual therapy and exercise. Outcomes The patient was seen a total of three visits, including the evaluation. Dry needling was utilized in two of her three visits. At discharge, she reported complete resolution of pain and altered sensation. Additionally, her scores on the shortened form of the Disability of the Arm, Shoulder, and Hand, Numerical Pain Rating Score, and Global Rating of Change exceeded the minimal clinically important difference (MCID). These outcomes were maintained at 2- and 12-month follow-up phone calls.

Lane, J. D. , B. G. Phillips-Bute and C. F. Piper.  1998. Caffeine raises blood pressure at work. 1998.  Psychosom Med  60(3):327-330. 

Lane JD, Pieper CF, Phillips-Bute BG et al. 2002. Caffeine affects cardiovascular and neuroendocrine activation at work and home. Psychosom Med 64(4):595-603. "Caffeine has significant hemodynamic and humoral effects in habitual coffee drinkers that persist for many hours during the activities of everyday life. Furthermore, caffeine may exaggerate sympathetic adrenal-medullary responses to the stressful events of normal daily life. Repeated daily blood pressure elevations and increases in stress reactivity caused by caffeine consumption could contribute to an increased risk of coronary heart disease in the adult population." [Doctors and patients need to seriously reevaluate the effect of caffeine as a perpetuating factor of sleep deprivation and central nervous system hyperstimulation.]

Lange G, Janal MN, Maniker A et al. 2011. Safety and Efficacy of Vagus Nerve Stimulation in Fibromyalgia: A Phase I/II Proof of Concept Trial. Pain Med. [Aug 3 Epub ahead of print]. "Side effects and tolerability were similar to those found in disorders currently treated with VNS (vagus nerve stimulation.) Preliminary outcome measures suggested that VNS may be a useful adjunct treatment for FM patients resistant to conventional therapeutic management, but further research is required to better understand its actual role in the treatment of FM."

Langevin HM. 2021. Fascia mobility, proprioception, and myofascial pain. Life (Basel). Jul 8;11(7):668. "The network of fasciae is an important part of the musculoskeletal system that is often overlooked. Fascia mobility, especially along shear planes separating muscles, is critical for musculoskeletal function and may play an important, but little studied, role in proprioception. Fasciae, especially the deep epimysium and aponeuroses, have recently been recognized as highly innervated with small diameter fibers that can transmit nociceptive signals, especially in the presence of inflammation. Patients with connective tissue hyper- and hypo-mobility disorders suffer in large number from musculoskeletal pain, and many have abnormal proprioception. The relationships among fascia mobility, proprioception, and myofascial pain are largely unstudied, but a better understanding of these areas could result in improved care for many patients with musculoskeletal pain."

Langevin HM. 2006.  Connective tissue: a body-wide signaling network?  Med Hypotheses. 66(6):1074-1077.  “Unspecialized ‘loose’ connective tissue forms an anatomical network throughout the body.  This paper presents the hypothesis that, in addition, connective tissue functions as a body-wide mechanosensitive signaling network.”   “Demonstrating the existence of a connective signaling network therefore may profoundly influence our understanding of health and disease.”  [This concept is increasingly important due to the finding of trigger points in so many types of tissue, and that at least MTPs have part in central sensitization.  DJS]

Langevin HM, Nedergaard M, Howe AK. 2013. Cellular control of connective tissue matrix tension. J Cell Biochem. Aug;114(8):1714-9. "The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function, and cancer."

Langford CF, Udvari Nagy S, Ghoniem GM. 2007.  Levator ani trigger point injections: an underutilized treatment for chronic pelvic pain.  Neurourol Urodyn 26(1):59-62.  “In the management of CPP, a non-surgical office-based therapy such as trigger point injections can be effective in selected patients.”

Laniosz V, Wetter DA, Godar DA. 2014. Dermatologic manifestations of fibromyalgia. Clin Rheumatol. [Jan 14 Epub ahead of print.] "Among these (over 800) Mayo Clinic fibromyalgia patients, various dermatologic conditions and cutaneous problems were identified, including hyperhidrosis in 270 (32.0 %), burning sensation of the skin or mucous membranes in 29 (3.4 %), and various unusual cutaneous sensations in 14 (1.7 %). Pruritus without identified cause was noted by 28 patients (3.3 %), with another 16 patients (1.9 %) reporting neurotic excoriations, prurigo nodules, or lichen simplex chronicus. Some form of dermatitis other than neurodermatitis was found in 77 patients (9.1 %). Patients with fibromyalgia may have skin-related symptoms associated with their fibromyalgia. No single dermatologic diagnosis appears to be overrepresented in this population, with the exception of a subjective increase in sweating."

Lanza. F. L., J. R. Codispoti and E. B. Nelson.  1998.  An endoscopic comparison of gastro-duodenal injury with over-the-counter doses of ketoprofen and acetaminophen.  Am J Gastro-enterol 93(7):1051-4.

Lapane KL, Quilliam BJ, Benson C et al. 2014. Impact of noncancer pain on health-related quality of life. Pain Pract. [Feb 27 Epub ahead of print.] "Among outpatients with various underlying causes of pain, the negative impact of pain on physical and mental health-related quality of life is significant."

Lark DS, Wasserman DH. 2017. Meta-fibrosis links positive energy balance and mitochondrial metabolism to insulin resistance. F1000Res. 6:1758. "While adipose tissue extracellular matrix remodeling has received considerable attention, it is becoming increasingly apparent that liver and skeletal muscle extracellular matrix remodeling also contributes to insulin resistance. In this review, we address recent advances in our understanding of energy balance, mitochondrial energetics, meta-inflammation, and meta-fibrosis in the development of insulin resistance." [This may be indicative of why insulin resistance is so common in patients with fibromyalgia and chronic myofascial pain and dysfunction. DJS]

Laroche F, Azoulay D, Trouvin AP et al. 2019. Fibromyalgia in the workplace: risk factors for sick leave are related to professional context rather than fibromyalgia characteristics - a French national survey of 955 patients. BMC Rheumatol. Oct 26;3:44. "We investigated factors associated with sick leave in professionally active women living with fibromyalgia…. In 5 months, we recruited 955 women, with a mean of 37 days of sick leave in the previous year: no sick leave (36%), up to 1 month (38%), 1 to 2 months (14%), more than 2 months (12%). In the groups displayed no differences in demographic characteristics, fibromyalgia symptoms, functional severity and psychological distress were observed. However, they differed in workplace characteristics, commute time, stress and difficulties at work, repetitive work, noisy conditions, career progression problems and lack of recognition, which were strong independent risk factors for longer sick leave. Sedentary positions, an extended sitting position, heavy loads, exposure to thermal disturbances and the use of vibrating tools did not increase the risk of sick leave…. Women with fibromyalgia frequently take sick leave, the risk factors for which are related to the workplace rather than fibromyalgia characteristics….Risk factors were found to be related to the workplace rather than fibromyalgia and personal characteristics. Workplace interventions should be developed for women with fibromyalgia."

Larrosa Pardo F, Bondesson E, Schelin MEC et al. 2019. A diagnosis of rheumatoid arthritis, endometriosis or IBD is associated with later onset of fibromyalgia and chronic widespread pain. Eur J Pain. [May 27 Epub ahead of print] "Widespread pain is a common comorbidity in several chronic diseases and is suspected to be caused by the underlying disease that has provoked a state of central sensitization.... The aim of this study was to investigate whether patients with rheumatoid arthritis (RA), endometriosis or inflammatory bowel disease (IBD) have a higher risk of developing widespread pain (fibromyalgia or chronic widespread pain [CWP]).... This study shows that RA, endometriosis and IBD are all risk factors for later fibromyalgia and chronic widespread pain, consistent with a hypothesis of central sensitization as an effect of a painful underlying condition." [It would be useful to know what percentage of patients had TrPs contributing to central sensitization. DJS]

Larson AA, Pardo JV, Pasley JD. 2013. Review of Overlap between Thermoregulation and Pain Modulation in Fibromyalgia. Clin J Pain. [Jul 24 Epub ahead of print]. "Fibromyalgia (FM) syndrome is characterized by widespread pain that is exacerbated by cold and stress but relieved by warmth. We review the points along thermal and pain pathways where temperature may influence pain. We also present evidence addressing the possibility that brown adipose tissue activity is linked to the pain of FM given that cold initiates thermogenesis in brown adipose tissue through adrenergic activity, whereas warmth suspends thermogenesis. Although females have a higher incidence of FM and more resting thermogenesis, they are less able to recruit brown adipose tissue in response to chronic stress than males. In addition, conditions that are frequently comorbid with FM compromise brown adipose activity making it less responsive to sympathetic stimulation. This results in lower body temperatures, lower metabolic rates, and lower circulating cortisol/corticosterone in response to stress-characteristics of FM. In the periphery, sympathetic nerves to brown adipose also project to surrounding tissues, including tender points characterizing FM. As a result, the musculoskeletal hyperalgesia associated with conditions such as FM may result from referred pain in the adjacent muscle and skin."

Larson, B., Bjork, J., Henriksson, K.J., Gerdle, B., Lindman, R. 2000. The prevalence of cytochrome oxidase negative and super-positive fibers and ragged red fibers in the trapezius muscle of female cleaners with and without myalgia and/or female healthy controls. Peripheral pain input from injuries, inflammation, or chronic work-related myalgia are probable sources of persistent nociceptive impulses could lead to a central sensitization.  Furthermore, once central sensitization develops, peripheral pain generators, such as myofascial trigger points, may lead to perpetuation and aggravation of central sensitization.

Latina R, Sansoni J, D'Angelo D et al. 2013. [Etiology and prevalence of chronic pain in adults: a Narrative Review.] Prof Inferm. 66(3):151-158. [Article in Italian] "The chronic nonmalignant pain is an underestimated epidemiologic health problem. It is a disease in its own right. It is one of the major reasons because patients use health service. The magnitude of chronic pain is in terms of human suffering and costs to society. The aim of this review is to identify the diagnosis and the prevalence of nonmalignant chronic pain in the adults….Excluding topics of headache, pain for pediatric and geriatric groups, cancer pain and disease-specific items. … We have obtained 7 articles. These epidemiological studies conducted in different part of the world, reported prevalence rates of chronic pain ranging from 16-53%. They show a high heterogeneity of results concerning diagnosis and methods. Although limited the number of articles, show the high complexity of the phenomenon."

Latysheva NV, Platonova AS, Filatova EG. 2019. [Temporomandibular disorder and cervicalgia: pathophysiology underlying the comorbidity with chronic migraine]. Zh Nevrol Psikhiatr Im S S Korsakova. 119(1):17-22. [Russian] "Myofascial pain was the most prevalent form of TMD in both EM (episodic migraine) and CM (chronic migraine)…. The higher prevalence of pain-related TMD and cervicalgia in CM population compared to EM and the general population was shown. In CM, myofascial pain and tenderness in the masticatory and neck muscles may be caused by central sensitization (CS) with no link to temporomandibular joint or spinal pathology. Myofascial TMD and neck muscle dysfunction are an integral part of CM pathophysiology underlying headache chronification."

Lauche R, Spitzer J, Schwahn B et al. 2016. Efficacy of cupping therapy in patients with the fibromyalgia syndrome-a randomized placebo controlled trial. Sci Rep. 6:37316. "Despite cupping therapy being more effective than usual care to improve pain intensity and quality of life, effects of cupping therapy were small and comparable to those of a sham treatment, and as such cupping cannot be recommended for fibromyalgia at the current time." Free PMC Article

Lauche R, Stumpe C, Fehr J et al. 2016. The effects of Tai Chi and neck exercises in the treatment of chronic non-specific neck pain: A randomized controlled trial. J Pain. [Jun 23 Epub ahead of print.] "This study aimed to test the efficacy of Tai Chi for treating chronic neck pain. Subjects with chronic non-specific neck pain were randomly assigned to 12 weeks of group Tai Chi or conventional neck exercises with weekly sessions of 75-90 minutes, or a wait-list control…. After 12 weeks Tai Chi participants reported significantly less pain compared to the wait list…. Group differences were also found for pain on movement, functional disability and quality of life compared to wait list. No differences were found for Tai Chi compared to neck exercises. Patients' satisfaction with both exercise interventions was high, and only minor side effects were observed."

Laulan J. 2016. Thoracic outlet syndromes. The so-called "neurogenic types". Hand Surg Rehabil. "Neurogenic thoracic outlet syndrome (TOS) is one of the most controversial pain syndromes of the upper limbs. The controversies revolve around both the diagnosis and treatment of the non-specific or subjective subtypes. Their diagnosis rests on a combination of history, suggestive symptoms and clinical examination. Proximal pain is primarily muscular in origin, while distal symptoms may be the result of intermittent nerve compression and/or myofascial pain syndrome. Stringent clinical criteria are required to confirm the diagnosis of subjective TOS. In reality, multiple factors can be entangled, with TOS being one element within a multifactorial pain disorder; any musculotendinous pathology of the upper limb and any peripheral nerve entrapment require screening for potential concomitant TOS. Surgery is indicated in most cases of true neurogenic TOS, whereas rehabilitation is the standard treatment for subjective TOS."

Lauretti GR. 2008. Mechanisms of analgesia of intravenous lidocaine. Rev Bras Anestesiol. 58(3):280-286.  “The final analgesic action of intravenous lidocaine is a reflection of its multifactorial action.  It has been suggested that its central sensitization is secondary to a peripheral anti-hyperalgic action on somatic pain and central on neuropathic pain, which result in the blockade of central hyperexcitability. The intravenous dose should not exceed the toxic plasma concentration of 5 microg mL(-1); doses smaller than 5 mg kg(-1), administered slowly (30 minutes), under monitoring, are considered safe.”

Laursen K, Sehgal N, Poliak-Tunis M et al. 2017. Regarding modulation of central sensitization following trigger point anesthetization in patients with chronic pain from whiplash trauma. Pain Med. [Oct 28 Epub ahead of print] The central pain from FM and other central sensitization states can be eased by dealing with TrPs.

Lautenbacher S. 2012. Experimental approaches in the study of pain in the elderly. Pain Med. 13 Suppl 2:S44-50. "The present review summarizes experimental data on age-related changes in pain processing. These data suggest an increase in pain threshold and a decrease in tolerance threshold, which both are dependent on the physical nature of the stressor, as well as a developing deficiency in endogenous pain inhibition, which might be paralleled by an enhanced disposition to central sensitization (stronger temporal summation). These findings are arranged in a model that allows for explaining the two seemingly divergent perspectives: age both dulls the pain sense and increases the prevalence of pain complaints. This model is based on the assumption that both excitatory and inhibitory processes are dampened with age but that the later processes age at a faster rate, leading to increasingly unbalanced pain excitation."

Lautenbacher S, Kunz M, Strata P et al. 2005.  Age effects on pain thresholds, temporal summation and spatial summation of heat and pressure pain.  “...somatosensory thresholds for non-noxious stimuli increase with age whereas pressure pain thresholds decrease and heat pain thresholds show no age-related changes.”

Lautenbacher S, Rollman GB, McCain GA. 1994.  Multi-method assessment of experimental and clinical pain in patients with fibromyalgia.  Pain 59(1):45-53.  There is increased pain responsiveness for any noxious stimuli in FM patients, including cold, heat, and electronic stimulation, although the latter was noted in the tender point regions.

Lavergne MR, Cole DC, Kerr K et al. 2010. Functional impairment in chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Can Fam Physician. 56(2):e57-65.  “The patient population was predominantly female (86.7%), with a mean age of 44.6 years. Seventy-eight patients had discrete diagnoses of 1 of MCS, CFS, or FM, while the remainder had 2 or 3 overlapping diagnoses. Most (68.8%) had stopped work, and on average this had occurred 3 years after symptom onset. On every Short Form-36 subscale, patients had markedly lower functional scores than population average values, more so when they had 2 or 3 of these diagnoses. Having FM, younger age at onset, and lower socioeconomic status were most consistently associated with poor function. CONCLUSION: Patients seen at the EHC demonstrated marked functional impairment, consistent with their reported difficulties working and caring for their homes and families during what should be their peak productive years. Early comprehensive assessment, medical management, and social and financial support might avoid the deterioration of function associated with prolonged illness. Education and information resources are required for health care professionals and the public, along with further etiologic and prognostic research.” [The loss to society, as well as to the patients and their families, is tremendous. More care must be taken to prevent these conditions and avoid these perpetuating factors.  Beginning symptoms must be pounced upon as a cat on a mouse, and care must be taken to avoid worsening of the conditions. DJS]

Lawson GE, Hung LY, Ko GD et al. 2011. A case of pseudo-angina pectoris from a pectoralis minor trigger point caused by cross-country skiing. J Chiropr Med. 10(3):173-178. "This case demonstrates the importance of differential diagnosis and mechanism of injury in regard to chest pain and that chiropractic management can be successful when addressing patients with chest wall pain of musculoskeletal origin."

Lawson K. 2016. Potential drug therapies for the treatment of fibromyalgia. Expert Opin Investig Drugs. 16:1-11. "Fibromyalgia (FM) is a common, complex chronic widespread pain condition characterized by fatigue, sleep disturbance and cognitive dysfunction. Treatment of FM is difficult, requiring both pharmacological and nonpharmacological approaches, with an empiric approach to drug therapy focused toward individual symptoms, particularly pain. The effectiveness of current medications is limited with many patients discontinuing use…. Modest improvement of health status in patients with FM has been observed with drugs targeting a diverse range of molecular mechanisms. No single drug, however, offered substantial efficacy against all the symptoms characteristic of FM. Identification of new and improved therapies for FM needs to address the heterogeneity of the condition, which suggests existence of patient subgroups, the relationship of central and peripheral aspects of the pathophysiology and a requirement of combination therapy with drugs targeting multiple molecular mechanisms."

Lawson VH, Grewal J, Hackshaw KV et al. 2018. Fibromyalgia syndrome and small fiber, early or mild sensory polyneuropathy. Muscle Nerve. [Mar 23 Epub ahead of print] "The FM-SFSPN subset of patients may be identified through sural and medial plantar sensory NCS and/or skin biopsy but cannot be identified by pain features and intensity."

Lean ME. 2000. Obesity: burdens of illness and strategies for prevention or management.  Drugs Today (Barc) 36(11):773-784.  Obesity is implicated as a perpetuating factor in low back pain, hypertension, metabolic syndrome, fatigue, dyspnea, and obstructive sleep apnea.

Leavitt F, Katz RS. 2015. Cross-sectional Neurocognitive Data Do Not Support a Transition From Fibrofog to Alzheimer Disease in Fibromyalgia Patients. J Clin Rheumatol. 21(2):81-85. Got fibrofog? From the Department of Behavioral Sciences and Section of Rheumatology, Department of Internal Medicine, Rush Medical College, Chicago, IL, comes welcome and comforting research. "The cognitive pattern of fibromyalgia appears distinct from that of Alzheimer's disease. Fibrofog is not associated with either episodic memory loss on standard tests of episodic memory or progressive cognitive decline. Patients with fibrofog remember personally experienced events termed episodic memory at a normal rate in quiet, distraction-free conditions. Patients with Alzheimer's disease do not. They forget the essential elements of short stories just read to them in environments free of distractions. In Alzheimer's disease, the brain mechanisms responsible for encoding personally experienced events into memory are irreversibly impaired. In fibrofog, the encoding mechanisms are intact. At the heart of memory loss in fibromyalgia is the inability to appropriately filter out relevant distractions. Encoding mechanisms that otherwise operate normally in forming episodic memories for everyday events in fibromyalgia appear to malfunction when 2 streams of information operate concurrently (relevant information and a source of distraction overlap). The findings should allay the worries of many with fibromyalgia who fear that fibrofog is the start of a dementing process."

Leavitt F, Katz RS. 2014. Cognitive dysfunction in fibromyalgia: Slow access to the mental lexicon. Psychol Rep. [Dec 24 Epub ahead of print.] "Lexical access speed, the time needed for the brain to access the catalogue of words in long-term memory, is assumed to provide a foundation for a broad array of cognitive operations. It was hypothesized that deficits in lexical speed are likely to play a central role in deficiencies in cognitive performance of patients with fibromyalgia, who as a group show deficits in lexical speed. This was tested in a sample of 209 patients with fibromyalgia and in 72 control patients with memory deficits…. Deficit in lexical access speed occurred at approximately twice the frequency (48.3% vs. 25.0%) in fibromyalgia. The average delay in speed of lexical access was 171 msec. in fibromyalgia and 163 msec. in controls….The premise that lexical access speed is disproportionately present in fibromyalgia and serves as a foundation for a wide array of cognitive operations is supported."

Leavitt F, Katz RS. 2011. Development of the Mental Clutter Scale. Psychol Rep. 109(2):445-452. "Mental fog is a core symptom of fibromyalgia. Its definition and measurement are central to an understanding of fibromyalgia-related cognitive disability. The Mental Clutter Scale was designed to measure mental fogginess. In an exploratory factor analysis of two different samples (n=128 and n=170), cognitive symptoms of fibromyalgia loaded on 2 dimensions: cognition and mental clarity. The mental clarity factor comprised 8 items with factor loadings greater than .60 and was named the Mental Clutter Scale. The factor stability of the new scale was good, internal consistency was .95, and test-retest reliability over a median of 5 days was .92. The 8-item scale is a quick measure of mental fog that provides clinicians with information about cognitive functioning in fibromyalgia."

Leavitt F, Katz RS. 2009.  Normalizing memory recall in fibromyalgia with rehearsal: a distraction-counteracting effect.  Arthritis Rheum. 61(6):740-744.  “In the absence of rehearsal, a source of distraction added to unrefreshed information signals a remarkable level of cognitive deficit in FMS that goes undetected by conventionally relied-upon neurocognitive measures.”

Leavitt F, Katz RS, Mills M et al. 2002.  Cognitive and dissociative manifestations in fibromyalgia.  J Clin Rheumatol. 8(2):77-84.  “These findings suggest that dissociation may play a role in FM symptom amplification and may aid in comprehending the regularity of cognitive symptoms.  Separating cases of fibrofog from cognitive conditions with actual brain damage is important.  It may be prudent to add a test of dissociation as an adjunct to the evaluation of FM patients in cases of suspected fibrofog.  Otherwise, test results may prove normal even in patients with disabling cognitive symptoms.”

Leavitt F, Katz RS. 2006.  Distraction as a key determinant of impaired memory in patients with fibromyalgia.  J Rheumatol. 33(1):127-132.  “The findings validate the perception of failing memory in patients with FM and are the first psychometric based evidence to our knowledge of short-term memory problems in FM linked to interference from a source of distraction.  Adding a source of distraction caused the majority of FM patients to retain new information poorly and may be integral to an understanding of FM memory problems.”

Leddy J, Baker JG, Haider MN et al. 2017. A physiological approach to prolonged recovery from sport-related concussion. J Athl Train. 52(3):299-308. "Ongoing symptoms reflect prolonged concussion pathophysiology or conditions such as migraine headaches, depression or anxiety, chronic pain, cervical injury, visual dysfunction, vestibular dysfunction, or some combination of these. In this paper, we focus on the physiological signs of concussion to help narrow the differential diagnosis of PCS in athletes…. Some athletes with PCS have exercise intolerance that may result from altered control of cerebral blood flow. Systematic evaluation of exercise tolerance combined with a physical examination of the neurologic, visual, cervical, and vestibular systems can in many cases identify one or more treatable postconcussion disorders. [Postconcussion symptoms may be much more varied and amplified in chronic pain patients. It is of importance that primary care providers and patients themselves recognize this. DJS]

Leddy JJ, Sandhu H, Sodhi V et al. 2012. Rehabilitation of concussion and post-concussion syndrome. Sports Health. 4(2):147-154. "Prolonged symptoms after concussion are called post-concussion syndrome (PCS), which is a controversial disorder with a wide differential diagnosis....Treatment approaches depend on the clinician's ability to differentiate among the various conditions associated with PCS. Early education, cognitive behavioral therapy, and aerobic exercise therapy have shown efficacy in certain patients but have limitations of study design. An algorithm is presented to aid clinicians in the evaluation and treatment of concussion and PCS and in the return-to-activity decision."

Lee B, Henderson LA, Rae CD et al. 2020. CRPS is not associated with altered sensorimotor cortex GABA or glutamate. eNeuro. [Jan 23 Epub ahead of print] "Complex regional pain syndrome is a debilitating chronic pain disorder that usually affects the limbs. It is associated with altered sensorimotor cortex function including reorganisation and reduced tactile acuity, which are thought to result from reduced on-going inhibition. However, we found that this pain condition is not associated with reduced on-going sensorimotor inhibition in the form of gamma-Aminobutyric acid concentration, the major inhibitory neurotransmitter in the brain. These findings strongly suggest that changes in sensorimotor function in individuals with complex regional pain syndrome are explained by factors other than neurotransmitter concentration."

Lee C, Liptan G, Kantorovich S et al. 2018. Association of Catechol-O-methyltransferase single nucleotide polymorphisms, ethnicity, and sex in a large cohort of fibromyalgia patients. BMC Rheumatol. Dec 12;2:38. "This is the largest study, to date, that examines demographic and genetic associations of FM in a diverse population. While pain sensitivity-associated COMT haplotypes were not found to be directly associated with FM diagnosis, the minor alleles that make up the COMT haplotypes were over-represented in the FM population, suggesting a role of COMT in FM. Future studies are needed to elucidate the exact role of COMT variation in widespread pain conditions, such as FM. Clinically, this information can be used to provide insight into the pathways underlying FM and to identify those at greater risk of developing FM." Free Article

Lee CJ, Levitt RC, Felix ER et al. 2017. Evidence that dry eye is a comorbid pain condition in a U.S. veteran population. Pain Rep. 2(6):e629. "Dry eye frequency increased with the number of pain conditions reported .... Ocular pain was most strongly associated with headache..., tension headache..., migraine..., temporomandibular joint dysfunction ..., pelvic pain..., central pain syndrome..., and fibromyalgia/muscle pain . Tear film dysfunction was most closely associated with osteoarthritis... and postherpetic neuralgia.... Dry eye, including both ocular pain and tear film dysfunction, is comorbid with pain conditions in this nationwide population, implying common mechanisms."

Lee CY, Kim EJ, Hwang DG et al. 2019. The effect of trigger point injections on pain in patients with advanced cancer. Korean J Fam Med. [Sep 6 Epub ahead of print] "It has been reported that in 62.5% of cases of incurable cancer pain, the complaint is due to myofascial pain syndrome….This study evaluated the efficacy of trigger point injections for alleviating pain in patients with advanced cancer….Twenty patients with advanced cancer who had a life expectancy of 6 months or less and had been diagnosed with myofascial pain syndrome were treated with trigger point injections. Prior to treatment, a Visual Analog Scale (VAS) was used to measure the resting pain level and discomfort upon application of pressure on the site of pain. These values were compared with last treatment measurements. The mean pre-treatment VAS scores for pain at rest and upon application of pressure on the pain site were 7.3 and 9.0, respectively. These scores decreased significantly to 1.95 and 3.2, respectively, after the treatment …." [Trigger points contribute to much chronic pain and dysfunction, and so much misery could be eased if care providers were trained. DJS]

Lee DG, Chang MC. 2017. Dorsal scapular nerve injury after trigger point injection into the rhomboid major muscle: A case report. J Back Musculoskelet Rehabil. [Aug 14 Epub ahead of print] "A 38-year-old man complained that his right shoulder functioned less optimally during push-up exercises after a trigger point injection 4 weeks prior. Physical examination revealed mildly reduced right shoulder retractor muscle strength compared with the left side…. The findings of the nerve conduction velocity test and electromyography indicated partial right dorsal scapular neuropathy. The nerve injury seemed to have been caused by the needle inserted during trigger point injection."

Lee DW, Lim CH, Han JY et al. 2016. Chronic pelvic pain arising from dysfunctional stabilizing muscles of the hip joint and pelvis. Korean J Pain. 29(4):274-276. "Chronic pelvic pain in women is a very annoying condition that is responsible for substantial suffering and medical expense. But dealing with this pain can be tough, because there are numerous possible causes for the pelvic pain such as urologic, gynecologic, gastrointestinal, neurologic, or musculoskeletal problems. Of these, musculoskeletal problem may be a primary cause of chronic pelvic pain in patients with a preceding trauma to the low back, pelvis, or lower extremities. Here, we report the case of a 54-year-old female patient with severe chronic pelvic pain after a transcutaneous electrical nerve stimulation (TENS) accident that was successfully managed with image-guided trigger point injections on several pelvic stabilizing muscles." Free PMC Article

Lee H, Xie L, Yu M et al. 2015. The effect of body posture on brain glymphatic transport. J Neurosci. 35(31):11034-11044. "The major finding of our study was that waste...was most efficient in the lateral position (compared with the prone position), which mimics the natural resting/sleeping position of rodents. Although our finding awaits testing in humans, we speculate that the lateral position during sleep has advantage with regard to the removal of waste products...." Free Article [This study is on rats, but may indicate a connection between glymphatic clearance and TrPs affecting the "drainage system". DJS]

Lee HJ, Choi E, Nahm FS et al. 2018. Prevalence of fibromyalgia in fourteen Korean tertiary care university hospital pain clinics. J Pain Res. 11:2417-2423. "Participants' demographic information and eleven comorbid measures (sleep disturbance, fatigue, irritable bowel syndrome, amnesia, hypothyroidism, headache, anxiety, depression, rheumatism, low back pain, and history of traffic accident) were also investigated via additional questionnaires. We recruited 1,233 outpatients (754 men and 479 women).... Patients with FM were more likely to have one or more of the eleven predetermined comorbid conditions. Patients who were female and who had a previous history of FM, sleep disturbance, headache, or a history of traffic accident were more likely to have FM.... FM, according to the modified 2010 ACR criteria, appears to be a common disorder among chronic pain patients referred to tertiary care university hospital pain clinics. Therefore, physicians treating pain should consider this prevalence of FM among pain clinic patients." Free Article [It would be useful to identify the percentage of these patients with TrPs. DJS]

Lee JKC, Law TYX, Shen L, et al. 2024. Extracorporeal shockwave therapy of the perineum for male patients with chronic pelvic pain syndrome: a pilot study. Prostate Int. 2024 Mar;12(1):27-34. "In terms of erectile function, improvement in the erectile function domain of International Index for Erectile Function was observed. There was also significant improvement in lower urinary tract symptoms assessed on International Prostate Symptom Score. There were no adverse events reported post treatment and during the follow-up period….ESWT improved pain and quality of life of male patients with CPPS.

Lee JW, Park HS. 2015. Relation of the factor to menstrual pain and musculoskeletal pain. J Exerc Rehabil. 11(2):108-111. "The purpose of the present study is to investigate the relationship between the regions of menstrual pain and of myofascial pain syndrome, which is the main cause of musculoskeletal pain, as well as to examine the changes and relationships among the menstrual pain-related factors, which are pain level, pain area, activity, appetite, mood, and sleeping pattern. The subjects were 13 sufferers of musculoskeletal pain and 17 non-sufferers. Pain diary and pain chart systems were used for the measurement of menstrual pain-related factors and musculoskeletal pain. Data were analyzed using repeated ANOVA. The results show that there are significant differences between the two groups in pain level, activity, and mood during menstruation periods.... The area of musculoskeletal pain and menstrual pain were found to be the same." Free PMC Article

Lee JY, Choi SH, Park KS et al. Comparison of complex regional pain syndrome and fibromyalgia: Differences in beta and gamma bands on quantitative electroencephalography. Medicine (Baltimore). 2019 Feb;98(7):e14452. "Complex regional pain syndrome (CRPS) and fibromyalgia (FM) share many features. Both can cause severe pain and are considered to have a mechanism of action, including dysfunction of the sympathetic nervous system. However, they have clinical differences in pain range and degree. The present study aimed to find neurophysiologic differences between CRPS and FM using quantitative electroencephalography (QEEG). Thirty-eight patients with CRPS and 33 patients with FM were included in the analysis. Resting-state QEEG data were grouped into frontal, central, and posterior regions to analyze for regional differences... There were no significant differences between 2 groups in the delta, theta, and alpha bands. The present findings show that the CRPS and FM groups differ mainly in the high frequency, which may reflect their distinct pathophysiology and symptomatology. Our study suggests that the QEEG differences can be clinically useful in assessing brain function in patients with CRPS and FM.

Lee KJ, Kim JH, Cho SW. 2005.  Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhea-predominant irritable bowel syndrome.  Aliment Pharmacol Ther. 22(10):981-988.  “Our results show that gabapetin reduces rectal sensory thresholds through attenuating rectal sensitivity to distension and enhancing rectal compliance in diarrhea-predominant irritable bowel syndrome patients.”   [This meshes with findings of central sensitization in IBS patients. DJS]

Lee LK, Ebata N, Hlavacek P et al. 2016. Humanistic and economic burden of fibromyalgia in Japan. J Pain Res. 9:967-978. eCollection. "Japanese adults with fibromyalgia experienced significantly poorer health-related quality of life and greater loss in work productivity and health care use than those without fibromyalgia, resulting in significantly higher costs. Improving the rates of diagnosis and treatment for this chronic pain condition may be helpful in addressing this considerable humanistic and economic burden." Free Article

Lee MJ, Chung YS. 2013. Spinal subarachnoid hematoma as a complication of an intramuscular stimulation: case report and a review of literatures. J Korean Neurosurg Soc. 54(1):58-60. "Intramuscular stimulation (IMS) is widely used to treat myofascial pain syndrome. IMS is a safe procedure but several complications have been described. To our knowledge, spinal subarachnoid hematoma has never been reported as a complication of an IMS. The authors have experienced a case of spinal subarachnoid hematoma occurring after an IMS, which was tentatively diagnosed as intracranial subarachnoid hemorrhage because of severe headache. Patient was successfully treated with surgery."

Lee MY, Lee HY, Yong MS. 2014. Characteristics of Cervical Position Sense in Subjects with Forward Head Posture. J Phys Ther Sci. 26(11):1741-1743. "The purpose of this study was to investigate the effect of forward head posture (FHP) on proprioception by determining the cervical position-reposition error. [Subjects and Methods]….This result implies that the change in the muscle length caused by FHP decreases the joint position sense. Also, proprioception becomes worse as FHP becomes more severe."

Lee SS, Yoon HJ, Chang HK et al. 2005.  Fibromyalgia in Behcet’s disease is associated with anxiety and depression, and not with disease activity.  Clin Exp Rheumatol. 23(4 Suppl 38):S15-19.  “FM (fibromyalgia) was very common among BD (Behcet’s Disease) patients and was associated with the presence of anxiety and depression, and not with disease activity.”  [Multiple invisible illnesses (especially if one or more is undiscovered and untreated for a number of years and causes a chronic pain state) have a greater chance to cause depression, and this must be taken into account. DJS]

Lee U, Kim M, Lee K et al. 2018. Functional brain network mechanism of hypersensitivity in chronic pain. Sci Rep. 8(1):243. "Fibromyalgia (FM) is a chronic widespread pain condition characterized by augmented multi-modal sensory sensitivity. Although the mechanisms underlying this sensitivity are thought to involve an imbalance in excitatory and inhibitory activity throughout the brain, the underlying neural network properties associated with hypersensitivity to pain stimuli are largely unknown. In network science, explosive synchronization (ES) was introduced as a mechanism of hypersensitivity in diverse biological and physical systems that display explosive and global propagations with small perturbations. We hypothesized that ES may also be a mechanism of the hypersensitivity in FM brains. To test this hypothesis, we analyzed resting state electroencephalogram (EEG) of 10 FM patients. First, we examined theoretically well-known ES conditions within functional brain networks reconstructed from EEG, then tested whether a brain network model with ES conditions identified in the EEG data is sensitive to an external perturbation. We demonstrate for the first time that the FM brain displays characteristics of ES conditions, and that these factors significantly correlate with chronic pain intensity. The simulation data support the conclusion that networks with ES conditions are more sensitive to perturbation compared to non-ES network. The model and empirical data analysis provide convergent evidence that ES may be a network mechanism of FM hypersensitivity." Free Article [This is a small study, but very interesting, and may provide some insight as to possible mechanisms of rapid increase in symptoms in instances such as migraine and trigger point cascades as well. DJS]

Lee YC. 2013. Effect and treatment of chronic pain in inflammatory arthritis. Curr Rheumatol Rep. 15(1):300. "Pain is the most common reason patients with inflammatory arthritis see a rheumatologist. Patients consistently rate pain as one of their highest priorities, and pain is the single most important determinant of patient global assessment of disease activity. Although pain is commonly interpreted as a marker of inflammation, the correlation between pain intensity and measures of peripheral inflammation is imperfect. The prevalence of chronic, non-inflammatory pain syndromes such as fibromyalgia is higher among patients with inflammatory arthritis than in the general population. Inflammatory arthritis patients with fibromyalgia have higher measures of disease activity and lower quality of life than inflammatory patients who do not have fibromyalgia. This review article focuses on current literature involving the effects of pain on disease assessment and quality of life for patients with inflammatory arthritis. It also reviews non-pharmacologic and pharmacologic options for treatment of pain for patients with inflammatory arthritis, focusing on the implications of comorbidities and concurrent disease-modifying antirheumatic drug therapy."

Lee YH, Kim JH, Song GG. 2014. Association between the COMT Val158Met polymorphism and fibromyalgia susceptibility and fibromyalgia impact questionnaire score: a meta-analysis. Rheumatol Int. [Jun 21 Epub ahead of print.] "This meta-analysis identified an association between fibromyalgia risk and the COMT Val158Met polymorphism as well as the FIQ score in fibromyalgia patients."

Leeb BF, Andel I, Sautner J et al.  2004.  The DAS28 in rheumatoid arthritis and fibromyalgia patients.  [Epub]  “Conclusion: The DAS28, as expected, proved to be inappropriate to express disease activity in FM patients.  DAS28 values for expressing disease activity in RA patients may be flawed by coexisting FM and should therefore be regarded with caution as high pain levels more than impaired mood may lead to higher total scores.”

Legier L. 2005.  Treatment of chronic low back pain incorporating active patient participation and chiropractic: a retrospective case report.  J Chiropr Med. 4(4):200-205.  “A 43-year-old female experienced severe right lumbar, right sacrum, and right acetabular pain and muscle spasms occurring after playing a vigorous tennis match 16 years earlier.”  “By the time of presentation she also experienced right arm and right upper back pain.  A lumbar MRI scan showed an L4/5 disc bulge.  Patrick’s, Yeoman’s and Kemp’s tests were positive on her right side.  She had an asymmetrical gait pattern with a right hip hike, lateral shift and rotation of the pelvis.  Weakness of the left gluteus maximus, gluteus medius, and right erector spinae muscles was present.  Motion palpation revealed several fixations.  There was tenderness to palpation of the right psoas muscle and a trigger point in the right iliacus muscle.”  “Incorporation of active patient participation seemed to be a significant factor in the resolution of the patient’s low back pain.  Active patient participation improved the quality of life for this patient.”  [It is a sad commentary that the patient had to endure so many years of pain and dysfunction before finding a care provider who could properly address the cause of her symptoms. DJS]

Lei X, Song X, Fan Y, et al. The role and potential mechanism of complement factor D in fibromyalgia development. J Pain Res. 2023 Dec 19:16:4337-4351. In summary, based on bioinformatic methods and big data mining we obtained a new target CFD for FM, and further experiments verified that CFD has significant inhibition of ATP-induced neuropathic pain.

Leinders M, Doppler K, Klein T et al. 2016. Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome. Pain. 157(11):2493-2503. "We confirmed previous findings of disturbed small fiber function and reduced intraepidermal nerve fiber density in subgroups of patients with FMS. We found 51 aberrantly expressed miRNAs in white blood cells of patients with FMS, of which miR-let-7d correlated with reduced small nerve fiber density in patients with FMS. Furthermore, we demonstrated miR-let-7d and its downstream target insulin-like growth factor-1 receptor as being aberrantly expressed in skin of patients with FMS with small nerve fiber impairment. Our study gives further evidence of small nerve fiber pathology in FMS subgroups and provides a missing link in the pathomechanism that may lead to small fiber loss in subgroups of patients with FMS."

Leite CMF, Profeta VLDS, Chaves SFN et al. 2019. Does exercise-induced muscle damage impair subsequent motor skill learning? Hum Mov Sci. 67:102504. "Motor skill learning is a fundamental aspect of human behavior based on the calibration of internal models via sensory information such as proprioception. Some conditions, as exercise-induced muscle damage (EIMD), disrupt proprioceptive information, and may cause learning impairment. … The EIMD group showed less accurate and consistent results on the long term (delayed posttest). Results confirmed our hypothesis that EIMD, a common condition in sports and in rehab practices, may hinder motor skill learning, possibly due to neurological aspects such as proprioceptive information, its relation to central nervous system reorganization and internal model consolidation."

Leitgeb N, Schrottner J. 2003.  Electrosensitibity and electromagnetic hypersensitivity.  Bioelectromagnetics 24(6):387-394.  Both electromagnetic hypersensitivity (developing health symptoms due to exposure of environmental electromagnetic fields) and electromagnetic sensibility (the ability to perceive electric and electromagnetic exposure) have been scientifically documented.  People with electromagnetic sensibility do not necessarily have electromagnetic hypersensitivity.

Lemming D, Graven-Nielsen T, Sörensen,Arendt-Nielsen L et al. 2012. Widespread pain hypersensitivity and facilitated temporal summation of deep tissue pain in whiplash associated disorder: An explorative study of women. J Rehabil Med. 44(8):648-657. "Widespread deep tissue pain hyperalgesia was evaluated in women with chronic whiplash associated disorder ...and controls ...using computerized cuff pressure algometry and hypertonic saline infusion.... The results indicated widespread hyperalgesia in chronic whiplash associated disorder and facilitated temporal summation outside the primary pain area, suggesting involvement of central sensitization."

Lenert ME, Szabo-Pardi TA, Burton MDD. Regulatory T-cells and IL-5 mediate pain outcomes in a preclinical model chronic muscle pain. Mol Pain. 2022 Jun 17;17448069221110691. "The experiments in this study provide novel evidence that downregulation of regulatory T-cells play a role in chronic muscle pain pathology in the acidic saline model of FM and that IL-5 signaling is a promising target for future development of therapeutics."

Leon-Llamas JL, Murillo-Garcia A, Villafaina S, et al. Relationship between kinesiophobia and mobility, impact of the disease, and fear of falling in women with and without fibromyalgia: A Cross-Sectional Study. Int J Environ Res Public Health. 2022 Jul 6;19(14):8257. "This study analyzes the kinesiophobia between women with fibromyalgia and apparently healthy women and investigates the relationship between kinesiophobia and physical fitness tests, fear of falling, and the impact of the fibromyalgia…. Women with fibromyalgia showed higher kinesiophobia scores, worse performance in mobility tests, and higher fear of falling than apparently healthy women. Kinesiophobia score is related to Timed Up and Go performance, the 10-step stair ascent, the fear of falling, and the impact of the disease in women with fibromyalgia." [These authors are using TrP-related parameters, not FM. They failed to consider TrPs affecting proprioceptor sense and autonomic concomitants predisposing to falls. There may be a failure to understand co-existing chronic myofascial pain and dysfunction in many fibromyalgia and/or kinesiophobia" studies. If someone gets hurt when they do a specific actions, it is logical to avoid that action. That is not phobia. Patients should not be judged by their medical care providers' lack of training. DJS]

Levene R, Gunther O, Rothkötter HJ et al. 2014. [Treatment of myofascial lumbar dorsal pain: Effective clinical diagnostics and therapy]. Schmerz. 28(6):573-583. [Article in German] "The results indicate that targeted treatment of muscles and fascia in patients with chronic back pain can lead to a reduction of pain symptoms. The consideration of the myofascial systems, particularly in relation to nonspecific back pain, could contribute to improving the treatment of pain and contribute to lowering costs."

Levesque A, Ploteau S, Michel F et al. 2020. Botulinum toxin infiltrations versus local anaesthetic infiltrations in pelvic floor myofascial pain: multicentre, randomized, double-blind study. Ann Phys Rehabil Med. [Jan 22 Epub ahead of print] "This study does not justify the use of botulinum toxin in the context of chronic pelvic pain with myofascial syndrome but does justify muscle injections with LA (local anaesthetic) alone."

Levine JD, Reichling DB. 2005.  Fibromyalgia: the nerve of that disease.  J Rheumatol Suppl. 75:29-37.  This paper categorizes FMS as “...a common, often debilitating and intractable, chronic, generalized pain condition.”  The authors suggest that there is altered activity in the subdiaphramatic vagus nerve that may be an integral part of this condition.  [This would mesh well with the findings of Linda Watkins and her research team regarding the development of central sensitization. DJS]

Levine TD, Saperstein DS. 2014. Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients. Clin Rheumatol. [Dec 24 Epub ahead of print.]"Fibromyalgia is a clinical syndrome that currently does not have any specific pathological finding to aid in diagnosis. Therefore, fibromyalgia is most likely a heterogeneous group of diseases with similar symptoms. Identifying and understanding the pathological basis of fibromyalgia will allow physicians to better categorize patients, increasing prospective treatment options, and improving potential therapeutic endeavors. Recent work has demonstrated that approximately 50 % of patients diagnosed with fibromyalgia have damage to their small unmyelinated nerve fibers. A skin punch biopsy is a sensitive and specific diagnostic test for this damage as a reduction in nerve fiber density allows for the diagnosis of small fiber neuropathy. Small fiber neuropathy is a disease with symptoms similar to fibromyalgia, but it often has a definable etiology. Identifying small fiber neuropathy and its underlying cause in fibromyalgia patients provides them with a succinct diagnosis, increases treatment options, and facilitates more specific studies for future therapeutics." [This is of concern, as fibromyalgia research indicates FM is a central nervous system dysfunction. This "test" may be indicative of myofascial trigger points or other co-existing condition. We need more research taking into consideration common co-existing illnesses that may be interfering with microcirculation. DJS]

Levy O, Amit-Vazina M, Segal R et al. 2015. Visual analogue scales of pain, fatigue and function in patients with various rheumatic disorders receiving standard care. Isr Med Assoc J. 17(11):691-696. "A total of 618 visits of 383 patients with inflammatory as well as non-inflammatory rheumatic disorders were analyzed. Fibromyalgia patients had significantly higher VAS scores compared to all other groups….patients with polymyalgia rheumatica demonstrated significantly lower VAS scores compared to all other groups of patients. Patients with psoriatic arthritis also demonstrated relatively low VAS scores. VAS scores were lower in patients with inflammatory disorders as compared to patients with non-inflammatory disorders….The findings emphasize the need to explore the underlying mechanisms of pain and fatigue in patients with non-inflammatory rheumatic disorders." Free Article

Levy O, Segal R, Maslakov I et al. 2016. The impact of concomitant fibromyalgia on visual analogue scales of pain, fatigue and function in patients with various rheumatic disorders. Clin Exp Rheumatol. [Apr 6 Epub ahead of print.] "Concomitant FM is common both among patients with inflammatory and patients with non-inflammatory rheumatic disorders. Concomitant FM has a remarkable impact on the severity of symptoms and, moreover, patients with concomitant FM exhibit extreme and significantly distinct levels of pain and fatigue which is as severe as that reported by patients with primary FM. It seems that fibromyalgic features dominate and become the main cause of morbidity in rheumatological patients with concomitant FM." [We are finally getting more research indicating that FM does not occur alone, and increase the level of pain and fatigue of other illnesses. DJS]

Lew J, Kim J, Nair P. 2020. Comparison of dry needling and trigger point manual therapy in patients with neck and upper back myofascial pain syndrome: a systematic review and meta-analysis. J Man Manip Ther. Sep 22;1-11. "Both DN and TPMT improve pain and function in the short to medium term. Neither is more superior than the other".

Lewin, D. S. and R. E. Dahl.  1999.  Importance of sleep in the management of pediatric pain. J Dev Behav Pediatr 20(4):244-52.

Lewis GK Jr., Langer MD, Henderson CR Jr. et al. 2013. Design and Evaluation of a Wearable Self-Applied Therapeutic Ultrasound Device for Chronic Myofascial Pain. Ultrasound Med Biol. [Jun 3 Epub ahead of print]. "Ultrasound therapy for pain and healing is a versatile treatment modality for musculoskeletal conditions that is used daily in rehabilitation clinics around the world. Our group designed and constructed a wearable, battery-operated, low-intensity therapeutic ultrasound (LITUS) device that patients could self-apply and operate during daily activity for up to 6 h. Thirty patients with chronic trapezius myofascial pain evaluated the LITUS system in a double-blind, placebo-controlled, 10-d study under institutional review board approval. While continuing their prescribed medication regimen, patients with the active device reported on average 1.94× reduction in pain and 1.5× improvement in health relative to placebo devices after 1 h of treatment. Both of these results were statistically significant …for the first 2 d of the study. Male patients reported the majority of benefit…. The study indicates that wearable, long-duration LITUS technology improves mobile access to drug-free pain relief."

Lewis JD, Wassermann EM, Chao W et al. Central sensitization as a component of post-deployment syndrome. NeuroRehabilitation. 31(4):367-372. "Many service members and veterans report chronic unexplained symptoms such as pain, fatigue and memory complaints, which have most recently been characterized as post-deployment syndrome (PDS). Chronic widespread pain is a component of this syndrome, producing significant disability and considerable health care costs. The similarity between the nature of these complaints and other medically unexplained illnesses such as fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome suggest that they may share a common mechanism. Here, we provide support for PDS as a consequence of pain and sensory amplification secondary to neuroplastic changes within the central nervous system, a phenomenon often termed central sensitization. We also discuss how factors such as stress and genetics may promote chronic widespread pain in veterans and service members who develop PDS." [These patients were not examined for chronic myofascial pain. DJS]

Lewit K, Olsanska S. 2004.  Clinical importance of active scars: abnormal scars as a cause of myofascial pain.  J Manipulative Physiol Ther. 27(6):399-402.  “The treatment of active scars can be of importance in a great number of cases; untreated, active scars are an important cause of therapeutic failure.  Treatment also widens the scope of manipulative therapy."

Lewit, K. and D. G. Simons.  1984.  Myofascial pain: relief by post-isometric relaxation. Arch Phys Med Rehabil 65(8):452-6. 

Li G, Yuan H, Zhang W. 2014. Effects of Tai Chi on health related quality of life in patients with chronic conditions: A systematic review of randomized controlled trials. Complement Ther Med. 22(4):743-755. "One of the characters of chronic illness is life-long condition with the deterioration in health related quality of life. Tai Chi has become a popular mind-body exercise and self-management strategy for patients with chronic conditions regarding its various physical and psychological effects…. Tai Chi appears to be safe and has positive effects on health related quality of life in patients with chronic conditions, especially for patients with disorders in Cardio-cerebrovascular and respiratory systems, and musculoskeletal system. However, as the delivery mood of Tai Chi provides multiply benefits, which part of the group provides the most benefit in improving quality of life is unclear. Due to the design limitations of previous studies, more larger and well-designed RCTs are needed to confirm the effects. And qualitative researches are warranted to explore how Tai Chi may work exactly from patients' own perspectives."

Li L, Stoop R, Clijsen R. etc. Criteria used for the diagnosis of myofascial trigger points in clinical trials on physical therapy: Updated systematic review. Clin J Pain. 2020 Aug 24. [Online ahead of print.] "Objective: To conduct an updated systematic review of diagnostic criteria for myofascial trigger points (MTrPs) used in clinical trials of physical therapy interventions from 2007 to 2019…. Conclusions: A noteworthy number of the included studies failed in properly reporting the MTrP diagnostic criteria. Moreover, high variability in the use of MTrP diagnostic was also observed. Spot tenderness, referred pain and local twitch response were the three most popular criteria (and the most frequently used combination). A lack of transparency in the reporting of MTrP diagnostic criteria is present in the literature."

Li LH, Huang QM, Barbero M et al. 2019. Quantitative proteomics analysis to identify biomarkers of chronic myofascial pain and therapeutic targets of dry needling in a rat model of myofascial trigger points. J Pain Res. 12:283-298. "Proteomics analysis may provide important information regarding the pathogenesis of chronic myofascial pain and the mechanisms underlying the treatment effects of dry needling. This study used a rat model of myofascial trigger points (MTrPs) to perform a proteomics analysis. Three biological replicate experiments were used to compare the proteomes of healthy control rats, a rat model of MTrP, MTrP model rats following dry needling of MTrPs, and MTrP model rats following dry needling of non-MTrPs. Tandem mass tag (TMT) labeling technology based on nanoscale liquid chromatography-tandem mass spectrometry was used. Hierarchical clustering, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction network analysis were performed to characterize the proteins. To validate the TMT results, three candidate biomarker proteins were verified using parallel reaction monitoring and Western blot analysis….A total of 2,635 proteins were identified. GO and KEGG enrichment analyses showed that the glycolysis/gluconeogenesis pathways played dominant roles in the pathogenesis of chronic myofascial pain. The three candidate biomarker proteins were the pyruvate kinase muscle isozyme (encoded by the PKM gene), the muscle isoform of glycogen phosphorylase (encoded by the PYGM gene), and myozenin 2 (encoded by the MYOZ2 gene). The validation results were consistent with the TMT results….This is the first proteomics study that has investigated the pathogenesis of chronic myofascial pain and the mechanisms underlying the treatment effects of dry needling in an in vivo rat model of MTrPs, which might promote our understanding of the molecular mechanisms underlying chronic myofascial pain."

Li RM, Franks RH, Dimmitt SG et al. 2011. Ideas and innovations: inclusion of pharmacists in chronic pain management services in a primary care practice. J Opioid Manag. 7(6):484-487. "Nonmalignant chronic pain management involves an ongoing process of complex evaluations including proper patient selection, proper prescribing, and careful monitoring. In the Pain Management Refill Clinic, patients are stabilized on an opioid regimen by either a pain specialist or a primary care physician (PCP). The PCP assumes long-term prescription of the regimen and proper follow-up. The inclusion of pharmacists in the management of patients suffering from chronic pain has allowed the physicians to improve opioid prescribing, documentation, and monitoring in accordance with chronic nonmalignant pain guidelines."

Li T, Chen X, Zhang C, Zhang Y et al. 2019. An update on reactive astrocytes in chronic pain. J Neuroinflammation. 16(1):140. "Chronic pain is a critical clinical problem with an increasing prevalence. However, there are limited effective prevention measures and treatments for chronic pain. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in both physiological and pathological conditions. Over the past few decades, a growing body of evidence indicates that astrocytes are involved in the regulation of chronic pain. Recently, reactive astrocytes were further classified into A1 astrocytes and A2 astrocytes according to their functions. After nerve injury, A1 astrocytes can secrete neurotoxins that induce rapid death of neurons and oligodendrocytes, whereas A2 astrocytes promote neuronal survival and tissue repair. These findings can well explain the dual effects of reactive astrocytes in central nervous injury and diseases…. This review provides updated information on the role of astrocytes in the regulation of chronic pain. In particular, we discuss recent findings about A1 and A2 subtypes of reactive astrocytes and make several suggestions for potential therapeutic targets for chronic pain." Free Article [Research, for some time, suggests activated glial cells are an important part of central sensitization states, but the vast majority of research money is still targeting neurons rather than glial cells. DJS]

Li W.W., Le Goascogne C., Ramauge M.  Deiodinases of thyroid hormones: induction in the sciatic nerve after injury.  Glia (Suppl 1):S89 [Abstract].

Li X, Luo M, Gong Y, et al. Altered brain activity and effective connectivity within the nonsensory cortex during stimulation of a latent myofascial trigger point. Neural Plast. 2022 Aug 12;2022:4416672. "The data investigated the latent MTrP-induced changes in brain activity and effective connectivity (EC) within the nonsensory cortex. The parameter wavelet amplitude (WA) was used to describe cortical activation, EC to show brain network connectivity, and main coupling direction (mCD) to exhibit the dominant connectivity direction in different frequency bands. An increasing trend of WA and a decreasing trend of EC values were observed in the PFC (Prefrontal cortex). The interregional mCD was primarily shifted from a unidirectional to bidirectional connection, especially from PFC to MC(motor cortex) or OL(occipital lobe), when responding to manual stimulation during the MTrP state compared with resting state and NMTrP (nonmyofascial trigger point) state in the intervals III, IV, and V. This study demonstrates that the nonsensory cortex PFC, MC, and OL can participate in the cortical reactions induced by stimulation of a latent MTrP. Additionally, the PFC shows nonnegligible higher activation and weakened regulation than other brain regions. Thus, the PFC may be responsible for the central cortical regulation of a latent MTrP.

Li XY, Wang JH, Wu C. 2018. Knowing the neuronal mechanism of spontaneous pain to treat chronic pain in the future. Adv Exp Med Biol. 1099:115-124. "Spontaneous pain is the major complain for the patients to see a doctor. Human imaging studies presented that spontaneous pain is mainly associated with activity changes in medial pain pathway, while broader brain regions were activated by allodynia pain. On behavioral level, temporally disassociation between the evoked pain and spontaneous pain was observed; these data gave a hint that the spontaneous pain and evoked pain may be mediated by different neuronal mechanisms. And more attentions should be paid to the spontaneous pain to treat the chronic pain in the future."

Li Y, Wu F, Wei J et al. 2020. Laser Moxibustion Alleviates Knee Osteoarthritis Pain by Inhibiting Spinal Microglial Activation-Mediated Neuroinflammation in Rats. Photobiomodul Photomed Laser Surg. [Jan 23 Epub ahead of print] "Central sensitization driven by glial activation-mediated neuroinflammation is recognized as a key mechanism in pain processing. Laser moxibustion using low-intensity laser irradiation of corresponding acupoints significantly relieves knee osteoarthritis (KOA) pain. … This study demonstrated that laser moxibustion at ST35 significantly alleviated MIA-induced KOA pain through inhibition of the microglial activation-mediated neuroinflammation, at least partially, by suppressing the production of proinflammatory cytokines, which may provide a potential analgesic target for KOA pain relief."

Li YH, Wang FY, Feng CQ et al. 2014. Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials. PLoS One. 9(2):e89304. "Massage therapy with duration ≥5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings."

Li Z, Yang Y, Dong C et al. 2018. The prevalence of suicidal ideation and suicide attempt in patients with rheumatic diseases: a systematic review and meta-analysis. Psychol Health Med. 8:1-12. "A total of 17 identified studies matched the inclusion criteria, involving 5174 participants with systemic lupus erythematosus (SLE), osteoarthritis (OA), rheumatoid arthritis (RA) and fibromyalgia (FM).... Meta-analysis showed that rheumatic diseases patients have high prevalence of SI (suicidal ideation) ...and SA (suicide attempts).... We also found the prevalence of SI and SA in females may be higher than in males. All of these indicated that rheumatologists should screen for SI and SA in their patients. Early appropriate intervention is therefore essential to promote the patients' good mental health."

Liboff AR. 2017. The electromagnetic basis of social interactions. Electromagn Biol Med. 36(2):177-181. "It has been established that living things are sensitive to extremely low-frequency magnetic fields at vanishingly small intensities, on the order of tens of nT. We hypothesize, as a consequence of this sensitivity, that some fraction of an individual's central nervous system activity can be magnetically detected by nearby individuals. Even if we restrict the information content of such processes to merely simple magnetic cues that are unconsciously received by individuals undergoing close-knit continuing exposure to these cues, it is likely that they will tend to associate these cues with the transmitting individual, no less than would occur if such signals were visual or auditory. Furthermore, following what happens when one experiences prolonged exposure to visual and like sensory inputs, it can be anticipated that such association occurring magnetically will eventually also enable the receiving individual to bond to the transmitting individual. One can readily extrapolate from single individuals to groups, finding reasonable explanations for group behavior in a number of social situations, including those occurring in families, animal packs, gatherings as found in concerts, movie theaters and sports arenas, riots and selected predatory/prey situations. The argument developed here not only is consistent with the notion of a magnetic sense in humans, but also provides a new approach to electromagnetic hypersensitivity, suggesting that it may simply result from sensory overload."

Lichtenstein A, Tiosano S, Amital H. 2017. The complexities of fibromyalgia and its comorbidities. Curr Opin Rheumatol. [Oct 16 Epub ahead of print] "A greater proportion of psychiatric and rheumatologic disorders are associated with FMS patients than the population. Consequently, physicians treating patients with either condition should keep in mind that these patients may have such comorbidities and should be treated accordingly."

Lichtenstein A, Tiosano S, Comaneshter DD, et al. 2022. A case-control analysis of the associations between fibromyalgia syndrome and osteoporosis. Isr Med Assoc J. 2022 Nov;24(11):737-740. This review found a significant correlation between fibromyalgia and osteoporosis and noted early detection and prevention measures to prevent complications.

Lichtenstein A, Tiosano S, Comaneshter D et al. 2018. Cross-sectional analysis of the associations between fibromyalgia and diabetes mellitus. Reumatologia. 56(5):275-278. "The fibromyalgia syndrome (FMS) is a chronic condition consisting of widespread musculoskeletal pain and tenderness together with mood and cognitive dysfunction. Diabetes mellitus (DM) is a common condition causing significant and detrimental morbidity and mortality…. DM was found to be more common amongst FMS patients compared to matched controls to suggest that the pathophysiology of DM might lead a patient to develop FMS. Consequently, physicians treating DM patients should be aware of the possible risk and asses for clinical signs of FMS in order to diagnose and treat it in time to better their patients' quality of life and disease management." Free Article [Since insulin resistance is so common a perpetuating factor in both FM and CMPD, and diet is the best way to control it, it is important to manage it early and well. DJS]

Lidbeck J. 2016. [Central sensitisation and chronic organ-related pain]. Lakartidningen. 25;113 [Article in Swedish]. Central sensitisation is an essential mechanism in chronic musculoskeletal pain. In recent years, increasing evidence has come to light suggesting that central sensitisation is also a cause of chronic organ-related pain. This has several important implications. One is the need for broader professional education in mechanism-based pain classification. Today, simple clinical diagnostic procedures are used for the identification of central sensitisation in chronic musculoskeletal disorders, and these may also prove useful in the classification of organ-related pain. The diagnosis of central sensitisation may also lead to a reduction in extensive investigations and recurrent surgical procedures. Information on central sensitisation (pain neurophysiology education) for patients with chronic musculoskeletal pain reduces their fear of pain and increases their self-reliance and coping. A similar therapeutic approach may also be useful in patients diagnosed with organ-related chronic pain.

Liedberg GM, Björk M. 2013. Symptoms of subordinated importance in fibromyalgia when differentiating working from non-working women. Work. [Mar 26 Epub ahead of print]. "The non-working (NW) women reported a significantly higher severity of symptoms compared with the working (W) women. The most important variable when differentiating the W from the NW women was social support from colleagues and employers. ...To change prevailing attitudes and values towards persons with a work disability, a process of active intervention involving staff is needed. Educating employers as to how a disability may influence a work situation, and the importance of social support, can be improved." [In the case of women who have such severe pain and other disabling pain and dysfunctions that they cannot work, is it necessary to find another reason that such women who aren't working have greater pain? Where is the logic here? DJS]

Liedberg GM, Björk M, Borsbo B. 2015. Self-reported nonrestorative sleep in fibromyalgia - relationship to impairments of body functions, personal function factors, and quality of life. J Pain Res. 8:499-505. "This cross-sectional descriptive study included 224 consecutive patients diagnosed at a specialist center…. Using sleep variables (sleep quality, waking up unrefreshed, and tiredness when getting up), we identified two subgroups - the good sleep subgroup and the bad sleep subgroup - of women with FM. These subgroups exhibited significantly different characteristics concerning pain intensity, psychological variables (depressed mood, anxiety, catastrophizing, and self-efficacy), impairments of body functions, and generic and health-related quality of life. The good sleep subgroup reported a significantly better situation, including higher employment/study rate. The bad sleep subgroup reported a greater use of sleep medication. Five variables determined inclusion into either a good sleep or a bad sleep subgroup: pain in the evening, self-efficacy, anxiety, and according to the Short Form health survey role emotional and physical functioning." Free PMC Article

Liedberg GM, Henriksson CM.2002.  Factors of importance for work disability in women with fibromyalgia: An interview study.  Arthritis Rheum 15:47(3):266-74. "The ability to remain at work depends not only on limitation in work capacity, but also on the capacity of society to adjust work environments and work tasks.  More individual solutions are needed to allow women with fibromyalgia to maintain work roles."

Lillefjell M, Haugan T, Martinussen P et al. 2013. Non-ketogenic, low carbohydrate diet predicts lower affective distress, higher energy levels and decreased fibromyalgia symptoms in middle aged females with fibromyalgia syndrome as compared to the western pattern diet. J Musculoskel Pain 21(4):311-319. The non-ketogenic, low-carbohydrate diet improved mood, energy levels and confusional states and other symptoms in patients with fibromyalgia syndrome. [Although the authors mentioned this diet as improvement of "functional" and "affective" symptoms, they may be treating co-existing insulin resistance. DJS]

Lima D, Pacheco-Barrios K, Slawka E, et al. The role of symptoms severity, heart rate, and central sensitization for predicting sleep quality in patients with fibromyalgia. Pain Med. 2023 Jun 14; Online ahead of print. "Symptom severity, fatigue, pain, and depression (but no central sensitization) are the main predictors of poor sleep quality. Heart rate changes independently predicted the sleep disturbance subdomain (the most affected one in our sample), suggesting an essential role of physical conditioning in modulating sleep quality in FMS patients."

Lima LV, Abner TS, Sluka KA. 2017. Does exercise increase or decrease pain? Central mechanisms underlying these two phenomena. J Physiol. [Mar 29 Epub ahead of print.] "Exercise is an integral part of the rehabilitation of patients suffering a variety of chronic musculoskeletal conditions, such as fibromyalgia, chronic low back pain and myofascial pain. Regular physical activity is recommended for treatment of chronic pain and its effectiveness has been established in clinical trials for people with a variety of pain conditions. However, exercise can also increase pain making participation in rehabilitation challenging for the person with pain. Animal models of exercise-induced pain have been developed and point to central mechanisms underlying this phenomena, such as increased activation of NMDA receptors in pain-modulating areas. Meanwhile, a variety of basic science studies testing different exercise protocols, show exercise-induced analgesia involves activation of central inhibitory pathways. Opioid, serotonin and NMDA mechanisms acting in rostral ventromedial medulla (RVM) promote analgesia associated with exercise. This review explores and discusses current evidence on central mechanisms underlying exercised-induced pain and analgesia."

Lin G, Zhao X, Wang W, et al. 2022. The relationship between forward head posture, postural control and gait: A systematic review. Gait Posture. 2022 Oct 14;98:316-329. "Forward head posture (FHP) is a common postural deviation. An increasing number of studies have reported that people with FHP present with impaired postural control and gait; however, there is conflicting evidence... Current Lin evidence supports an association between FHP and a detrimental alteration in limits of stability, performance-based balance, and cervical proprioception. Instead of simply indicating impaired overall balance, the findings of this review indicate that a reduction in specific aspects of the postural control requires to be clarified in clinical evaluation for individuals with FHP, which would facilitate the planning and application of appropriate interventions to prevent dysfunctions and disability."

Lin MT, Chen HS, Chou LW et al. 2011. Treatment of attachment trigger points in the gluteal muscles to cure chronic gluteal pain: a case report. J Musculoskel Pain. 19(1):31-34. "Chronic myofascial pain syndrome in the gluteal region can be caused by both lumbar facet joint lesion and attachment TrPs of the involved muscles. It is necessary to eliminate the underlying etiological lesions appropriately in order to provide long-term relief of myofascial pain." [A significant number of patients diagnosed with fibromyalgia and/or chronic myofascial pain who have severe pain in spite of strong medication probably have spinal pathomorphologies. There are a number of non-surgical treatments to relieve the pain and decrease central sensitization, such as facet injection and epidural injection. These treatments can buy time, because frequency specific microcurrent can treat these spinal pathomorpholgies once the severe central pain is relieved. This would eliminate a lot of pain, and save a lot of money in disability and surgery. In an ideal world, these would have been prevented. Right now, we must treat what we have, and it is good to have documentation of facet injection helping associated TrPs. DJS]

Lin SY, Neoh CA, Huang YT et al. 2010. Educational program for myofascial pain syndrome. J Altern Complement Med. 16(6):633-640. "Sixty-two (62) patients with a 3-month or longer history of MPS… were randomized to an experimental group (n = 32) or a control group (n = 30). Both groups underwent trigger-point dry needling and muscle-stretch exercise regimen for passively stretching the affected muscles to their normal lengths; the experimental group then watched an 8-minute multimedia instructional video about MPS with supplemental handouts…..Compared to the control group, the experimental group had significantly less interference of pain, lower intensity of present pain, and least pain (p < 0.05)….The findings emphasize the importance of including patient education programs in MPS intervention."'

Lin, T. Y. , M. J. Teixeira, A. A. Fischer, F. G. Barboza, S. T. Immura, R. Mattar Jr. 1997. Work-related musculoskeletal disorders. Phys Med Rehab Clin N Am (Philadelphia): ****113-117.

Lin WC, Shen CC, Tsai SJ et al. 2017. Increased risk of myofascial pain syndrome among patients with insomnia. Pain Med. [Feb 11 Epub ahead of print.] "Patients with insomnia had a higher risk of developing myofascial pain syndrome than controls. This study adds to the understanding of the complex relationship between sleep disturbance and pain."

Lin YC, Kuan TS, Hsieh PC et al. 2012. Therapeutic Effects of Lidocaine Patch on Myofascial Pain Syndrome of the Upper Trapezius: A Randomized, Double-Blind, Placebo-Controlled Study. Am J Phys Med Rehabil. [Jul 30 Epub ahead of print]. "The 5% lidocaine patch may be helpful for relieving pain and reducing associated neck disability for a period of longer than one wk for treating patients with trigger points in the upper trapezius."

Lind BK, Lafferty WE, Tyree PT et al. 2007.  Use of complementary and alternative medicine providers by fibromyalgia patients under insurance coverage.  Arthritis Rheum. 57(1):71-76.  Even though there were an increased number of health care visits with more CAM use by the most ill patients, the use of CAM was not associated with higher overall cost.  “Until a cure for FMS is found, CAM (complementary and alternative medicines) providers may offer an economic alternative for patients with FMS seeking symptomatic relief.”

Linder MW, Valdes R Jr. 2001.  Genetic mechanisms for variability in drug response and toxicity.  J Anal Toxicol. 25(5):405-413.  This article gives four examples of how genetic mechanisms can affect drug action and reaction.

Lindsetmo RO, Stulberg J. 2009.  Chronic abdominal wall pain – a diagnostic challenge for the surgeon.  Am J Surg. 198(1):129-134.  Chronic abdominal wall pain is common, occurring in about 30% of patients with chronic abdominal pain.  It is frequently caused by trigger points in the fascia, but is usually misdiagnosed, leading to unnecessary testing and procedures, even surgery.

Lindgren, M., B. Eckert, G. Stenberg and C.-D. Agardh.  1996.  Restitution of neurophysiological functions, performance, and subjective symptoms after moderate insulin-induced hypoglycemia in non-diabetic men.  Diabetic Medicine 13:218-225.  was fast.

Linnemann A, Kappert MB, Fischer S et al. 2015. The effects of music listening on pain and stress in the daily life of patients with fibromyalgia syndrome. Front Hum Neurosci. 30;9:434."Listening to music, especially with the intent to improve relaxation or relieve stress, improved the perception of pain control in females with FM. This was unrelated to modification of the stress response system. Music did not affect pain intensity." Free PMC Article

Linton, S. J., A. L. Hellsing and D. Andersson.  1993.  A controlled study of the effects of an early intervention on acute musculoskeletal pain problems.  Pain 54(3):353-9.

Lipman, A. G.  1987.  Effects of smoking on drug therapy.  Modern Medicine 55:185-186.  The impact of smoking on drug absorption, metabolism, and action.

Lipman MD, Hess DE, Werner BC et al. 2017. Fibromyalgia as a predictor of Complex Regional Pain Syndrome after distal radius fracture. Hand (N Y). Oct 1:1558944717735949. "While the basis of the association between fibromyalgia and CRPS is unknown, our data suggest that it could serve as a useful predictor of CRPS risk, promoting increased vigilance for CRPS symptoms and earlier recognition and treatment, thereby improving patient outcomes."

Liporaci FM, Mourani MM, Riberto M. 2019. The myofascial component of the pain in the painful shoulder of the hemiplegic patient. Clinics (Sao Paulo). 74:e905. "These results demonstrate that the myofascial component of pain should be considered in post-stroke shoulder pain and that its treatment may be a pathway for the rapid and long-lasting relief of symptoms.... Trigger point blockade with lidocaine can reduce pain perception in spastic hemiplegic shoulder in as much as 50% of stroke survivors for four months." [TrPs can cause or contribute to symptoms in many chronic illnesses. DJS]

Liptan G, Mist S, Wright C et al. 2013. A pilot study of myofascial release therapy compared to Swedish massage in fibromyalgia. J Bodw Mov Ther. 17(3):365-370. This small study, with 8 women with FM having myofascial release and 4 having Swedish massage, 90 minutes each for four weeks, indicates that localized pain areas that can lead to central sensitization improved more with myofascial release. This can be important as research indicates that peripheral pain generators are responsible for FM central sensitization. As the study states, larger and more varied studies are needed. [It would be good to compare myofascial release with specific trigger point myotherapy, and with them both used in conjunction. It has been my experience that Swedish massage can help calm the central sensitization, and works well in combination with the other two techniques. We need to work to get these covered by insurance. DJS]

Liptan GL. The widespread myofascial pain of fibromyalgia is sympathetically maintained and immune mediated. J Bodyw Mov Ther. 2023 Jul;35:394-399. "Although immune system modulation may become an important treatment tool in FM, direct manual treatments that lessen myofascial inflammation and tension must not be neglected. Myofascial release therapy significantly reduces FM pain, with residual benefits even after the conclusion of treatment. Self-myofascial release techniques and gentle stretching programs also ease fibromyalgia pain, as do trigger point injections and dry-needling."

Liptan GL. 2010.  Fascia: a missing link in our understanding of the pathology of fibromyalgia.  J Bodyw Mov Ther. 14(1):3-12.  This is a very interesting study and a promising one.  Until quite recently, FM researchers were unaware of myofascial TrPs and myofascial practitioners were largely unaware of the central sensitization of FM and the need to modify therapies to accommodate it when it occurs in their patients.  FM is the amplifier.  TrPs are the pain generators.  There may be other pain generators, but the TrPs in the fascia (myofascia and other wise) are there and generating symptoms.  There are many of us patients with FM and CMP, and our needs cannot be met until researchers understand the complexity that both of these conditions together can create.  It is refreshing to see that the bridge is finally being built. DJS]

Lipworth L, Holmich LR, McLaughlin JK. 2011. Silicone breast implants and connective tissue disease: no association. Semin Immunopathol. [Jan 10 Epub ahead of print]. "...cosmetic breast implants are not associated with a subsequent increased occurrence of individual CTDs (connective tissue diseases) or all CTDs combined, including fibromyalgia. Moreover, there is no credible evidence for the conjectured excess of 'atypical' CTD among women with cosmetic breast implants, or of a rheumatic symptom profile unique to these women. No increased risk of CTDs is evident in women with extracapsular ruptures in two studies, which evaluated risk by implant rupture status, and no consistent association has been observed between silicone breast implants and a variety of serologic markers or autoantibodies."

Lisboa LL, Sonehara E, Oliveira KC et al. 2015. [Kinesiotherapy effect on quality of life, sexual function and climacteric symptoms in women with fibromyalgia]. Rev Bras Reumatol. [Apr 24 Epub ahead of print.] [Article in Portuguese] "The pelvic floor kinesiotherapy promotes a positive effect in the domains of quality of life, sexual function and climacteric symptoms in women with and without fibromyalgia in the climacteric period; however, fibromyalgia seems to be a limiting factor to achieve better results in some of the aspects evaluated." Free Article [The subjects were not evaluated for co-existing TrPs. DJS]

Lisi AJ, Breuer P, Gallagher RM et al. 2015. Deconstructing chronic low back pain in the older adult - step by step evidence and expert-based recommendations for evaluation and treatment: Part II: Myofascial pain. Pain Med. [Jun 18 Epub ahead of print.] "We present an algorithm and supportive materials to help guide the care of older adults with MP, an important contributor to chronic low back pain (CLBP). Addressing any perpetuating factors should be the first step of managing MP. Patients should be educated on self-care approaches, home exercise, and the use of safe analgesics when indicated. Trigger point deactivation can be accomplished by manual therapy, injection therapy, dry needling, and/or acupuncture….The algorithm presented gives a structured approach to guide primary care providers in planning treatment for patients with MP as a contributor to CLBP."

Lisinski P, Huber J. 2016. Evolution of muscles dysfunction from myofascial pain syndrome through cervical disc-root conflict to degenerative spine disease. Spine (Phila Pa 1976). [May 18 Epub ahead of print.] "The explanation for cervical pain origin should be based on results from chosen clinical and neurophysiological studies in correlation with neuroimaging findings. Only applying several clinical and neurophysiological tests together makes it possible to differentiate patients with different etiological reasons of pain at cervical spine."

Liska D. J. 1998. The Detoxification Enzyme Systems. Alt Med Rev 3(3):187-198.

Littlejohn GO, Guymer EK, Ngian GS. 2016. Is there a role for opioids in the treatment of fibromyalgia? Pain Manag. [Jun 14 Epub ahead of print.] "The use of opioids for chronic pain has increased significantly due to a combination of the high patient burden of pain and the more widespread availability of a range of long-acting opioid preparations. This increased opioid use has translated into the care of many patients with fibromyalgia. The pain mechanism in fibromyalgia is complex but does not seem to involve disturbance of opioid analgesic functions. Hence, there is general concern about the harms in the absence of benefits of opioids in this setting. There is no evidence that pure opioids are effective in fibromyalgia but there is some evidence that opioids with additional actions on the norepinephrine-related pain modulatory pathways, such as tramadol, can be clinically useful in some patients. Novel actions of low-dose opioid antagonists may lead to better understanding of the role of opioid function in fibromyalgia."

Liu A, Chedid V, Wang XJ et al. 2020. Clinical presentation and characteristics of pelvic floor myofascial pain in patients presenting with constipation. Neurogastroenterol Motil. Apr 13:e13845. "In constipated patients, PFMP (pelvic floor myofascial pain) is highly associated with RED (rectal evacuation disorder). Its presence provides a valuable clue regarding the etiology of a patient's constipation; it should be assessed in all patients with constipation and should also be an additional target for management."

Liu HY, Fuh JL, Lin YY et al. 2015. Suicide risk in patients with migraine and comorbid fibromyalgia. Neurology. Aug 21.[Epub ahead of print] "Patients with migraine and comorbid FM had higher headache frequency and headache-related disability, poor sleep quality, and were more depressed/anxious than those with migraine only…. Suicidal ideation and attempts were reported in 27.3% and 6.9% of patients with migraine, respectively, and were higher in patients with comorbid FM than in those without…. In addition, comorbidity of FM was associated with a higher suicide risk in 3 different migraine subgroups, i.e., migraine without aura, migraine with aura, and chronic migraine."

Liu HY, Lee PL, Chou KH, et al. Brain morphometry changes with fatigue severity in fibromyalgia. Clin Exp Rheumatol. 2022 Sep 6. Online ahead of print. "This study investigated brain morphometry changes associated with fatigue severity in fibromyalgia (FM)…. The thalamus and the right inferior temporal cortex are implicated in the manifestation of fatigue severity in FM. Future therapeutic strategies targeting these regions are worthy of investigation."

Liu L, Wu ZH, Huang QM, et al. Clinical observations in treatment of lower extremity varicose veins with trigger points acupuncture. Phlebology. 2023 Dec;38(10):675-682. Objectives: To observe the effect of the acupuncture of myofascial trigger points (MTrPs) in the treatment of lower extremity varicose veins (LEVVs). Methods: Overall, 260 patients with LEVVs participated in this study…. The MTrPs in the lower extremities were localized in accordance with the classification of LEVVs and treated by MTrPs acupuncture combined with self-massage and self-stretching. The interval between each treatment was 2 weeks to 1 month, depending on needling pain tolerance of each patient…. Conclusions: In some patients, MTrP acupuncture could cure LEVVs and its accompanying symptoms. These LEVVs are probably caused by fascia tension as a pre-pathology induced by the MTrPs.

Liu Q, Huang Q, Liu L, et al. Efficacy of dry needling under EMG guidance for myofascial neck and shoulder pain: A randomized clinical trial. J Pain Res. 2022 Aug 8;15:2293-2302. "DN under needle EMG guidance technique exhibited greater improvements in maintenance of improvement of pain and lower SEA value than the DN group due to sufficient MTrPs inactivation."

Liu S, Liu L, Lu X, et al. 2024. Effect of sympathetic blockade on spontaneous discharge and the H-Reflex at myofascial trigger points in rats. J Pain Res. 2024 Mar 27:17:1299-1311…. Myofascial trigger points (MTrPs) are the main cause of myofascial pain syndrome (MPS), and patients with MPS also have symptoms of sympathetic abnormalities…. Data were collected on peak inversion spontaneous potentials (PISPs) and the H-reflex-evoked electromyography during spontaneous discharge at the MTrPs before and after sympathetic blockade…. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate were significantly higher in the MTrPs group than in the non-MTrPs group…. The changes before and after sympathetic blockade in the MTrPs group were significant, and the amplitude, duration, and amplitude-to-duration ratio of the PISPs potentials were lower after the blockade…. MTrPs and sympathetic nerves interact with each other forming a specific relationship. MTrPs sensitize sympathetic nerves, and sympathetic nerve abnormalities affect local muscle myoelectric hyperactivity, leading to MTrPs.

Liu T, Ji RR. 2013. New insights into the mechanisms of itch: are pain and itch controlled by distinct mechanisms? Pflugers Arch. [May 1 Epub ahead of print]. "Itch and pain are closely related but distinct sensations. They share largely overlapping mediators and receptors, and itch-responding neurons are also sensitive to pain stimuli….Chronic itch results from dysfunction of the immune and nervous system and can manifest as neural plasticity despite the fact that chronic itch is often treated by dermatologists. While differences between acute pain and acute itch are striking, chronic itch and chronic pain share many similar mechanisms, including peripheral sensitization (increased responses of primary sensory neurons to itch and pain mediators), central sensitization (hyperactivity of spinal projection neurons and excitatory interneurons), loss of inhibitory control in the spinal cord, and neuro-immune and neuro-glial interactions. Notably, painful stimuli can elicit itch in some chronic conditions (e.g., atopic dermatitis), and some drugs for treating chronic pain are also effective in chronic itch."

Liu XG. Normalization of neuroinflammation: A new strategy for treatment of persistent pain and memory/emotional deficits in chronic pain. J Inflamm Res. 2022 Sep 9;15:5201-5233. "Emerging evidence has demonstrated that the neuroinflammation, characterized by overproduction of pro-inflammatory cytokines and glial activation, is reliably detected in humans and animals with chronic pain, and is sufficient to induce persistent pain and memory/emotional deficits. The abnormal expression of ion channels and pathological synaptic plasticity in spinal dorsal horn and in hippocampus are resulting from neuroinflammation. The neuroinflammation is initiated and maintained by the interactions of circulating monocytes, glial cells and neurons. Obviously, unlike infectious diseases and cancer, which are caused by pathogens or malignant cells, chronic pain is resulting from alterations of cells and molecules which have numerous physiological functions. Therefore, normalization (counterbalance) but not simple inhibition of the neuroinflammation is the right strategy for treating neuronal disorders. Currently, no such agent is available in clinic. While experimental studies have demonstrated that intracellular Mg2+ deficiency is a common feature of chronic pain in animal models and supplement Mg2+ are capable of normalizing the neuroinflammation, activation of upregulated proteins that promote recovery, such as translocator protein (18k Da) or liver X receptors, has a similar effect. In this article, relevant experimental and clinical evidence is reviewed and discussed."

Liu Z, Cappola AR, Crofford LJ et al. 2014. Modeling Bivariate Longitudinal Hormone Profiles by Hierarchical State Space Models. J Am Stat Assoc. 109(505):108-118. "The hypothalamic-pituitary-adrenal (HPA) axis is crucial in coping with stress and maintaining homeostasis. Hormones produced by the HPA axis exhibit both complex univariate longitudinal profiles and complex relationships among different hormones. Consequently, modeling these multivariate longitudinal hormone profiles is a challenging task." These authors propose a model to deal with interactive hormone balances. "Application of the proposed method to a study of chronic fatigue syndrome and fibromyalgia reveals that the relationships between adrenocorticotropic hormone and cortisol in the patient group are weaker than in healthy controls".

Liu ZJ, Yamagata K, Kuroe K et al. 2000.  Morphological and positional assessment of TMJ components and lateral pterygoid muscle in relation to symptoms and occlusion of patients with temporomandibular disorders.  J Oral Rehabil 27(10):860-874.  “These findings suggest that TMJ internal derangements are more related to the positional changes or spatial relationships of TMJ components but less to the individual morphologies of TMJ osseous structures, disc and LP (lateral pterygoid), as well as specific clinical symptoms and occlusal factors...” 

Llamas-Ramos R, Pecos-Martin D, Gallego-Izquierdo T et al. 2014. Comparison of the Short-Term Outcomes between Trigger Point Dry Needling Versus Trigger Point Manual Therapy for the Management of Chronic Mechanical Neck Pain: A Randomized Clinical Trial. J Orthop Sports Phys Ther. 30:1-34. "The results of this clinical trial suggest that 2 sessions of TrP-DN and TrP manual therapy resulted in similar outcomes in terms of pain, disability and cervical range of motion. Those in the TrP-DN group experienced greater improvements in PPT (pressure pain thresholds) over the cervical spine."

Lluch E, Nijs J, De Kooning M. 2015. Prevalence, incidence, localization, and pathophysiology of myofascial trigger points in patients with spinal pain: A systematic literature review. J Manipulative Physiol Ther. [Sep 18 Epub ahead of print.] "Myofascial trigger points are a prevalent clinical entity, especially in patients with neck pain….Compelling evidence supports local mechanisms underlying MTrPs. Future research should unravel the relevance of central mechanisms and investigate the incidence of MTrPs in patients with spinal pain."

Lobbezoo F, Visscher CM, Naeije M. 2004.  Impaired health status, sleep disorders, and pain in the craniomandibular and cervical spinal regions.  Eur J Pain 8(1):23-30.  “Both musculoskeletal pain in the trigemino-cervical area and widespread body pain are associated with an increased impairment of health status.  Also, sleep disorders are frequently found in patients with chronic pain in the craniomandibular and cervical spinal regions as well as in patients with widespread pain.  The more painful areas there are, the likelier it is that sleep disorders are present.”

Lobo CP, Pfalzgraf AR, Giannetti V et al. 2014. Impact of invalidation and trust in physicians on health outcomes in fibromyalgia patients. Prim Care Companion CNS Disord. 16(5). "Patients with fibromyalgia have reported experiencing discouragement, rejection, suspicion, and stigma during their encounters with health care professionals.… The aim of this study was to assess fibromyalgia patients' self-reported quality of life (QoL) and pain based on the following: perceptions of physician attitudes, trust in physicians, perceptions of medical professionals, type of treatment, and various demographic variables….Invalidation, trust in physician, and use of complementary medicine can have significant impact on QoL and pain in fibromyalgia. Further research in more representative fibromyalgia samples may help confirm findings." Free PMC Article

Lodahl M, Treister R, Oaklander AL. 2017. Specific symptoms may discriminate between fibromyalgia patients with vs. without objective test evidence of small-fiber polyneuropathy. Pain Rep. 13(1):e633. "Multiple studies now confirm that ~40% of patients with fibromyalgia syndrome meet diagnostic criteria for small-fiber polyneuropathy (SFPN) and have objective pathologic or physiologic evidence of SFPN, whereas 60% do not.... Among patients with fibromyalgia, most symptoms overlap between those with or without confirmed SFPN. Symptoms of dysautonomia and paresthesias may help predict underlying SFPN. The reason to screen for SFPN is because-unlike fibromyalgia-its medical causes can sometimes be identified and definitively treated or cured." [This study did not assess patients for trigger points, and they may have autonomic concomitants and cause parathesias. DJS]

Loeser JD. 2005.  Quo Vadis. Poena.  J Musculoskeletal Pain 13(3).  This editorial pinpoints some problems in the development of the field of chronic pain management.  One is the use of pain clinics as dumping grounds for complex cases.  Much of chronic pain is preventable, but it is not being prevented.  “Chronic illness will become the major health care issue in the 21st century, as the population ages and infectious diseases are better treated.”  “...we will need pain managements who have a broad overview of the diagnostic and therapeutic strategies that will provide the best possible outcomes.”  “Payers and providers will need to recognize that chronic pain is like diabetes: cure is not the goal.  Instead, management with the goal of minimizing morbidity, improving function, and containing costs is the optimal outcome.”

Loeser JD, Cahana A. 2013. Pain medicine versus pain management: ethical dilemmas created by contemporary medicine and business. Clin J Pain. 29(4):31-316. "The world of health care and the world of business have fundamentally different ethical standards. In the past decades, business principles have progressively invaded medical territories, leading to often unanticipated consequences for both patient and providers. Multidisciplinary pain management has been shown to be more effective than all other forms of health care for chronic pain patient; yet, fewer and fewer multidisciplinary pain management facilities are available in the United States.…We call for increased pin educational experiences for all types of health care providers and the separation of business concepts from pain-related health care." "Despite the talk about evidence-based medicine…the primary driving force behind changes in health care has become economics. …Chronic pain management has not done well in such an environment….chronic pain patients suffer from this more than most other patient groups."

Loeser, RF, Shakoor, N. 2003.  Aging or osteoarthritis: which is the problem?  Rheum Dis Clin North Am 29(4):653-673.  These authors realize that OA is not an inevitable part of getting old, and that the progression of structural deterioration in OA may be prevented by improving neuromuscular function.  Structural damage does not always correspond to joint deterioration, and proprioception is often involved, as is muscle weakness and lack of balance.  What is missing in this article is often at the heart of these things: myofascial trigger points.

Loevinger BL, Muller D, Alonso C et al. 2007.  Metabolic syndrome in women with chronic pain.  Metabolism 56(1):87-93.  “Women with chronic pain from fibromyalgia are at an increased risk for metabolic syndrome...”

Loftus CG, Ebbert JO, Aakre CA, et al. 2021. Creation of a multispecialty clinic for patients with central sensitization-based chronic pain conditions. Mayo Clin Proc Innov Qual Outcomes. Dec 23;6(1):45-54. "Our clinic model provides a framework for the treatment of patients with debilitating centrally sensitized conditions and future expansion of virtual care delivery models to better meet patient care and educational needs."

Loggia ML, Berna C, Kim J et al. 2014. Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia. Arthritis Rheum. 66(1):203-12. "In this study we investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain such as anticipation of pain and of pain relief….FMRI was performed on 31 FM patients and 14 controls while they received cuff pressure pain stimuli on their leg, calibrated to elicit a pain rating of ~50/100. During the scan, subjects also received visual cues informing them of impending pain onset (pain anticipation) and pain offset (relief anticipation)….Patients exhibited less robust activations during both anticipation of pain and anticipation of relief within regions commonly thought to be involved in sensory, affective, cognitive and pain-modulatory processes. In healthy controls, direct searches and region-of-interest analyses in the ventral tegmental area (VTA) revealed a pattern of activity compatible with the encoding of punishment: activation during pain anticipation and pain stimulation, but deactivation during relief anticipation. In FM patients, however, VTA activity during pain and anticipation (of both pain and relief) periods was dramatically reduced or abolished….FM patients exhibit disrupted brain responses to reward/punishment. The VTA is a source for reward-linked dopaminergic/GABAergic neurotransmission in the brain and our observations are compatible with reports of altered dopaminergic/GABAergic neurotransmission in FM. Reduced reward/punishment signaling in FM may relate to the augmented central processing of pain and reduced efficacy of opioid treatments in these patients."

Loh-Doyle JC, Stephens-Shields AJ, Rolston R, et al. Predictors of male sexual dysfunction in urologic chronic pelvic pain syndrome (UCPPS), other chronic pain syndromes, and healthy controls in the multidisciplinary approach to the study of chronic pelvic pain (MAPP) research network. J Sex Med. 2022 Dec 1;19(12):1804-1812. "A multidisciplinary approach that addresses the identified risk factors for SD may improve overall QoL in males with UCPPS…. When compared to healthy controls and patients with other chronic pain conditions, males with UCPPS experience higher degrees of SD, including erectile and ejaculatory dysfunction."

Lombard L., Augustyn M.N., Ascott-Evans B.H.  The metabolic syndrome — pathogenesis, clinical features and management.  Cardiovasc J S Afr 13(4):181-6.  “The metabolic syndrome is a highly prevalent clinical entity, which is often overlooked and may have far-reaching health implications to the patient.  Up to 80% of patients with the metabolic syndrome die as a result of cardiovascular complications.  Insulin resistance is the central component of this complex syndrome and should be appropriately addressed to ensure the best possible outcome for our patients.”

Lommel K, Kapoor S, Bamford J et al. 2009. Juvenile primary fibromyalgia syndrome in an inpatient adolescent psychiatric population. Int J Adolesc Med Health. 21(4):571-579. “Juvenile primary fibromyalgia is highly prevalent in an adolescent inpatient psychiatric unit. This possibility should be taken into consideration when chronic complaints of pain are expressed by patients in this setting, especially in those who have conduct-related issues. The connection between JPFS and abuse history requires further investigation.” [It is hoped that more studies will be done on identifying early warning signs of fibromyalgia and chronic myofascial pain.  If awareness of the importance of symptoms such as unrestorative sleep and growing pain becomes recognized, perhaps we can keep some of these patients from developing chronic pain conditions. DJS]

Long, D. M., M. BenDebba, W. S. Torgerson, R. J. Boyd, E. G. Dawson, R. W. Hardy, J. T. Robertson, G. W. Sypert and C. Watts.  1996.  Persistent back pain and sciatica in the United States: patient characteristics.  J Spinal Disord 9(1):40-58.

Lopez-Sola M, Pujol J, Wager TD et al. 2014. Altered fMRI responses to non-painful sensory stimulation in fibromyalgia patients. Arthritis Rheumatol. [Sep 15 Epub ahead of print.] "Patients reported increased subjective sensitivity (increased unpleasantness) in response to multisensory stimulation in daily life. FMRI revealed that patients showed reduced task-evoked activation in primary/secondary visual and auditory areas and augmented responses in the insula and anterior lingual gyrus. Reduced responses in visual and auditory areas were correlated with subjective sensory hyper-sensitivity and clinical severity measures….FM patients showed strong attenuation of brain responses to non-painful events in early sensory cortices, accompanied by an amplified response at later stages of sensory integration in the insula. These abnormalities are associated with core fibromyalgia symptoms, suggesting that they may be part of the pathophysiology of the disease."

Lopez-Sola M, Woo C.W, Pujol J et al. 2017. Towards a neurophysiological signature for fibromyalgia. Pain. 158(1):34-47. Fibromyalgia lacks a defining objective test. These researchers studied the various areas of the brain for the difference between fibromyalgia patients and people without fibromyalgia. They found "augmented responses in the insula/operculum, posterior cingulate, and medial prefrontal regions and reduced responses in the primary/secondary sensory cortices, basal ganglia, and cerebellum.... Enhanced NPS responses partly mediated mechanical hypersensitivity and correlated with depression and disability...; FM-pain and multisensory responses correlated with clinical pain.... The study provides initial characterization of individual patients with FM based on pathophysiological, symptom-related brain features. If replicated, these brain features may constitute objective neural targets for therapeutic interventions. The results establish a framework for assessing therapeutic mechanisms and predicting treatment response at the individual level." They were able to differentiate the neurophysiological signature (NPS) in fibromyalgia patients from the others over 90% of the time. "In agreement with previous observations...and considering the validation properties of the NPS, the results provide evidence of augmented pain-specific responses in FM, consistent with peripheral/central sensitization."

Lorduy KM, Liegey-Dougall A, Haggard R et al. 2013. The Prevalence of Comorbid Symptoms of Central Sensitization Syndrome among Three Different Groups of Temporomandibular Disorder Patients. Pain Pract. [Jan 22 Epub ahead of print]. "Myofascial TMD is characterized by a high degree of comorbidity of symptoms of CSS and associated emotional distress." [Patients with TMD should be assessed for myofascial pain due to trigger points, fibromyalgia, and other possible co-existing conditions, and distinction must be made between a general use of the term "myofascial pain" to mean TMJ and myofascial pain due to trigger points. DJS]

Lorenz, J., H. Beck and B. Bromm.  1997.  Cognitive performance, mood and experimental pain before and during morphine-induced analgesia in patients with chronic non-malignant pain. Pain 73(3):369-375.

Loretan S, Duvoisin B, Scolozzi P. 2011. Unusual fatal petrositis presenting as myofascial pain and dysfunction of the temporal muscle. Quintessence Int. 42(5):419-422. "Petrositis is a rare and severe complication of acute otitis media and mastoiditis.... We report here the unusual case of an 86-year-old man who presented with a handicapping myofascial pain and dysfunction syndrome of the right temporal muscle as a heralding manifestation of an unusual form of petrositis. The patient progressively developed a retropharyngeal abscess, a right sphenoid sinusitis, and fatal meningitis..... This case demonstrated that (1) myofascial pain and dysfunction syndrome that does not respond to conventional treatments may suggest an unusual etiology and warrant further medical investigations and a detailed medical history and that (2) petrositis can manifest itself with atypical clinical symptoms and radiologic signs."

Lorton D, Lubahn CL, Estus C et al. 2006.  Bidirectional communication between the brain and the immune system: implications for physiological sleep and disorders with disrupted sleep.  Neuroimmunomodulation. 13(5-6):357-374.  “The central nervous system (CNS) modulates immune function by signaling target cells of the immune system through autonomic and neuroendocrine pathways.  Neurotransmitters and hormones produced and released by these pathways interact with immune cells to alter immune functions, including cytokine production.  Cytokines produced by cells of the immune and nervous systems regulate sleep.  Cytokines released by immune cells, particularly interleukin-1beta and tumor necrosis factor-alpha, signal neuroendocrine, autonomic, limbic and cortical areas of the CNS to affect neural activity and modify behaviors (including sleep), hormone release and autonomic function.  In this manner, immune cells function as a sense organ, informing the CNS of peripheral events related to infection and injury.  Equally important, homeostatic mechanisms, involving all levels of the neuroaxis, are needed, not only to turn off the immune response after a pathogen is cleared or tissue repair is completed, but also to restore and regulate natural diurnal fluctuations in cytokine production and sleep.”  [This shows the interactivity of sleep dysfunction and immune dysfunction, common interactive diagnoses in patients with FM and CMP.  DJS]

Loscher W, Iglseder B. 2017. [Polyneuropathy in the elderly]. Z Gerontol Geriatr. [Apr 28 Epub ahead of print] [Article in German] "The peripheral nervous system is subject to changes during the aging process, e.g., deep tendon reflexes decrease, as does proprioception. Polyneuropathies, on the other hand, need to be distinguished from age-related changes as independent diseases with etiologies similar to those at younger ages. Etiologies includes metabolic disorders, primary inflammatory polyneuropathies, and systemic disorders. Neuropathies associated with diabetes, malignancy, and monoclonal gammopathies appear to be more common in older patients. Using a systematic approach, it is possible to establish a specific diagnosis in the majority of cases. Since polyneuropathies contribute to reduced mobility in the elderly, an assessment of functional skills is mandatory. Polyneuropathy therapy is primarily based on the treatment of underlying conditions and neuropathic pain management. Physiotherapy and rehabilitation target pain relief and maintaining activities of daily living." [This excellent article is a reminder for primary care providers to search for the cause of the symptom, and not be content with labeling it. Adequate treatment depends on the cause of the neuropathy. Please don't forget to include the common possibility of trigger point nerve entrapment. DJS.]

Lotaif AC, Mitrirattanakul S, Clark GT. 2006.  Orofacial muscle pain: new advances in concept and therapy.  J Calif Dent Assoc. 34(8):625-630.  “The probable mechanisms underlying chronic myogenous pains and trigger points phenomena are discussed.  Treatment options of the myogenous masticatory pain conditions including physical medicine modalities, as well as several types of pharmacologic agents, are presented.”    

Lotsch J, Geisslinger G, Tegeder I. 2009.  Genetic modulaton of the pharmacological treatment of pain.  Pharmacol Ther. [Jul 15 Epub ahead of print].  “Inadequately treated acute and chronic pain remains a major cause of suffering and dissatisfaction in pain therapy.  A cause for the variable success of pharmacologic pain therapy is the different genetic disposition of patients to develop pain or to respond to analgesics.  The patient’s phenotype may be regarded as the result of synergistic or antagonistic effects of several genetic variants concomitantly present in an individual.  Variants modulate the risk of developing painful disease or its clinical course (e.g., migraine, fibromyalgia, low back pain).  Other variants modulate the perception of pain….”  “Other polymorphisms alter pharmacokinetic mechanisms controlling the local availability of active analgesic molecules at their effector sites (e.g., decreased CYP2D6 related prodrug activation of codeine to morphine).  In addition, genetic variants may alter pharmacodynamic mechanisms controlling the interaction of the analgesic molecules with their target structures (e.g., opioids receptor mutations).  Finally, opioids dosage requirements may be increased depending on the risk of drug addiction….”  [This information is important for care providers and for patients to understand.  It may explain much of the variance of response to medications.  Sadly, genetics are not often taken into consideration when drawing up treatment plans.  This can not only increase long-term cost, it can greatly add to the possibility of multiple drug treatment failures.  DJS]

Lotsch J, Skarke C, Liefhold J et al. 2004.  Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives.  Clin Pharmacokinet. 43(14):983-1013.  Genetics can affect analgesic response to opioids (some patients may need higher doses to achieve the desired analgesia), affect metabolism of opioids, or cause drug reactions. 

Loucks TM, De Nil LF. 2006.  Anomalous sensorimotor integration in adults who stutter: a tendon vibration study.  Neurosci Lett. [May 11 Epub ahead of print]  “AWS (adults who stutter) use proprioceptive information less efficiently than normal speakers, which could interfere with sensorimotor integration during speech production.”  [This study did not evaluate patients for myofascial TrPs, which can often cause proprioceptive dysfunction, although it does mention that movement dysfunction is often associated with stuttering.  Some cases of stuttering may be related to myofascial TrPs, but studies are needed on this.  DJS]

Lourenco S, Costa L, Rodrigues AM et al. 2015. Gender and psychosocial context as determinants of fibromyalgia symptoms (fibromyalgia research criteria) in young adults from the general population. Rheumatology (Oxford). [May 14 Epub ahead of print.] "In young adulthood, psychological distress was particularly consistent in predicting SSS (symptom severity score) and may become useful as a red flag for the establishment of clinical disease."

Louter MA, Bosker JE, van Oosterhout WP et al. 2013. Cutaneous allodynia as a predictor of migraine chronification. Brain. [Sep 29 Epub ahead of print]. "Cutaneous allodynia is a risk factor for migraine chronification and may warrant preventive treatment strategies."

Lovati C, Mariotti C, Giani L et al. 2013. Central sensitization in photophobic and non-photophobic migraineurs: possible role of retino nuclear way in the central sensitization process. Neurol Sci. 34 Suppl 1:133-135. "Overall, these findings suggest that light stimulation may contribute to central sensitization of pain pathways in migraineurs, possibly contributing to progression into chronic forms. The possible connections underlying this type of sensitization are offered by the recently published data on a non-image-forming visual retino-thalamo-cortical pathway which may allow photic signals to converge on a thalamic region which is selectively activated during migraine headache."

Lovy, M. R., G. Starkebaum and S. Uberoi. 1996. Hepatitis C infection presenting with rheumatic manifestations: a mimic of rheumatoid arthritis. J Rheumatol 23(6):979-983.

Low LA, Schweinhardt P. 2012. Early Life Adversity as a Risk Factor for Fibromyalgia in Later Life. Pain Res Treat. 2012:140832. "This paper discusses risk factors from early life that may increase the occurrence or severity of FM in later life: pain experience during neonatal life causes long-lasting changes in nociceptive circuitry and increases pain sensitivity in the older organism; premature birth and related stressor exposure cause lasting changes in stress responsitivity; maternal deprivation affects anxiety-like behaviors that may be partially mediated by epigenetic modulation of the genome-all these adult phenotypes are strikingly similar to symptoms displayed by FM sufferers. In addition, childhood trauma and exposure to substances of abuse may cause lasting changes in developing neurotransmitter and endocrine circuits that are linked to anxiety and stress responses."

Lowe JC, Yellin J, Honeyman-Lowe G. 2006.  Female fibromyalgia patients: lower resting metabolic rates than matched healthy controls.  Med Sci Monit. 12(7):CR282-289.  This study indicates that FMS patients have a low metabolic rate, adjusted for patient fat percentage differential.  The study also reiterates what other research has found: that TSH, FT(4) and FT(3) values are not reliable indicators in FMS patients.


Lowe, J.C., Honeyman-Lowe, G. 1999. Ultrasound treatment of trigger points: differences in technique for myofascial pain syndrome and fibromyalgia patients.  This is a report of clinical experience described in terms of an experimental approach without presentation of hard data. The details of treatment depend strongly on what the patient feels.  The caveat that FMS patients are prone to be hyperreactive to ultrasound therapy and need to be treated less vigorously is consistent with their strong reaction to other treatments and life experiences.  It takes much more skill and gentleness to successfully treat MTrPs of FMS patients than uncomplicated MTrPs.

Lowe, J. C. and G. Honeyman-Lowe.  1998.  Facilitating the decrease in fibromyalgic pain during metabolic rehabilitation: an essential role for soft tissue therapies.  J Bodywork &Movement Therapies 2(4):208-217.

Lowe, J. C., M .E. Cullum, L. H. Graf Jr., J. Yellin. 1997.  Mutations in the c-erbA beta gene: do they underlie euthyroid fibromyalgia?  Med Hypo 48 (2): 125-135.

Lu S, Song L, Wang D et al. 2019. White matter hyperintensity and cognitive impairments in chronic insomniacs. Euroreport. [Apr 18 Epub ahead of print] "Abnormal sleep architecture and white matter hyperintensities (WMHs) may be involved in cognitive impairment. There is little evidence on the connections between WMHs and chronic insomnia disorder (CID). Therefore, we evaluated the severity of WMHs and polysomnography parameters as well as cognitive tests to explore the underlying connections. There was no significant difference in sex, age, or educational attainment (years) between the two groups. The data showed significant decreases in total sleep time, sleep efficiency, and percentage of time spent in stage non-rapid eye movement sleep 3 in the CID group, but this group also showed prolonged sleep latency and increased percentages of time spent in stages non-rapid eye movement sleep 1 and non-rapid eye movement sleep 2 and wake after sleep onset. Moreover, chronic insomniacs showed poor performance on the attention, intelligence, and memory tests, as well as visual recognition and visual regeneration. Importantly, WMHs were observed to be associated with sleep latency, percentage of time spent in stage non-rapid eye movement sleep 1, and percentage of time spent in stage non-rapid eye movement sleep 3. In conclusion, our findings suggest that there are certain underlying correlations between WMHs and sleep architecture. Abnormal sleep architecture and WMHs could be involved in the impairment of cognitive function in CID. However, it remains unclear whether WMHs are a pre-existing abnormality or a consequence of CID." [White matter hyperintensity is common in FM patients, as is abnormal sleep architecture. DJS]

Lu X, Hui-Chan CW, Tsang WW. 2012. Tai Chi, arterial compliance, and muscle strength in older adults. Eur J Prev Cardiol. [Apr 4 Epub ahead of print]. "Aerobic exercise can alleviate the declines in arterial compliance common in older adults. However, when combined with strength training, aerobic exercise may not reduce arterial compliance….Tai Chi practitioners showed significantly better haemodynamic parameters than the controls as indexed by larger and small artery compliance. They also demonstrated greater eccentric muscle strength in both knee extensors and flexors….The findings of better muscle strength without jeopardizing arterial compliance suggests that Tai Chi could be a suitable exercise for older persons to improve both cardiovascular function and muscle strength."

Lu XH1, Chang XL1, Liu SL et al. 2020. Ultrasound-guided inactivation of trigger points combined with muscle fascia stripping by liquid knife in treatment of postherpetic neuralgia complicated with abdominal myofascial pain syndrome: A prospective and controlled clinical study. Pain Res Manag. May 17;2020:4298509. "About 57% of PHN (postherpetic neuralgia) patients with mild to moderate pain are complicated with MPS, (myofascial pain syndrome) and ultrasound-guided inactivation of MTrPs with dry and wet needling can effectively treat PHN patients complicated with LMPS. However, patients with PHN complicated with AMPS (abdominal myofascial pain syndrome) need to be treated with ultrasound-guided MTrPs inactivation combined with muscle fascia stripping by liquid knife as soon as possible."

Luan S, Zhu ZM, Ruan JL et al. 2019. Randomized trial on comparison of the efficacy of extracorporeal shock wave therapy and dry needling in myofascial trigger points. Am J Phys Med Rehabil. 98(8):677-684. "The extracorporeal shock wave therapy is as effective as dry needling for relieving pain, improving function, and reducing shear modulus for patients with myofascial trigger points after a series of three treatments."

Lubkowska A, Radecka A, Bryczkowska I et al. 2018. Changes in the bioelectric activity of the trapezius muscle following the thermal effect of red light and infrared radiation. J Back Musculoskelet Rehabil. 31(4):645-656. "The study included 29 volunteers of whom the spontaneous and voluntary bioelectric activity of the trapezius muscle was evaluated using surface electromyography (value of average amplitude and frequency), before and immediately after a 15-minute irradiation. Additionally, the range of motion of the cervical spine and trigger points pain sensitivity to the pressure were assessed."No statistically significant changes in the pain sensitivity threshold and the range of motion after the irradiation was applied. On the other hand, a 15-minute exposure to radiation induced an increase in the value of average amplitude of rest-related as well as exercise-related potentials and an increase in the average value of frequency of the right side biopotentials at rest and of both sides for active elevation." [Infrared devices may help TrPs.]

Lucas KR, Rich PA, Polus BI. 2010. Muscle activation patterns in the scapular positioning muscles during loaded scapular plane elevation: The effects of Latent Myofascial Trigger Points. Clin Biomech (Bristol, Avon). [Jul 26 Epub ahead of print]. Latent myofascial trigger points can cause major dysfunction and must be taken seriously.

Lucas KR, Rich PA, Polus BI. 2007.  Do latent trigger points affect muscle activation patterns?  J Musculoskel Pain 15 (Supp 13):30 item 49.  [Myopain 2007 Poster]  “LTrPs (latent trigger points) alter the timing of muscle activation in common movement patterns suggesting that they should be treated.  Mechanisms that might mediate the effects observed are proposed.”  [Latent MTPs cause muscle dysfunction and restriction of range of motion, and may affect the way muscle function groups work together.  Care must be taken not to equate MTPs only with pain.  The dysfunction caused must be taken as seriously. DJS]

Lucas N, Macaskill P, Irwig L et al. 2009.  Reliability of physical examination for diagnosis of myofascial trigger points: a systematic review of the literature.  Clin J Pain. 25(1):80-89.  This article was based on review of literature.  Myofascial medicine takes time, training and experience.  Most care providers do not have these.   This must change. DJS]

Ludwig DS. 2003. Diet and development of the insulin resistance syndrome.  Asia Pac J Clin Nutr 12 Suppl:S4.  “Among modifiable factors including weight loss and exercise, dietary composition appears to have an important effect on development of IRS.  The available evidence suggests that IRS, and therefore diabetes and cardiovascular disease, can be prevented by a high fiber/low glycemic index diet containing dairy products and a higher amount of unsaturated fat than currently recommended.”

Luedtke K, Boissonnault W, Caspersen N et al. 2016. International consensus on the most useful physical examination tests used by physiotherapists for patients with headache: A Delphi study. Man Ther. 23:17-24. "Eleven tests are suggested as a minimum standard for the physical examination of musculoskeletal dysfunctions in patients with headache." These were: "… manual joint palpation, the cranio-cervical flexion test, the cervical flexion-rotation test, active range of cervical movement, head forward position, trigger point palpation, muscle tests of the shoulder girdle, passive physiological intervertebral movements, reproduction and resolution of headache symptoms, screening of the thoracic spine, and combined movement tests."

Lukkahatai N, Walitt B, Deandres-Galiana EJ et al. 2018. A predictive algorithm to identify genes that discriminate individuals with fibromyalgia syndrome diagnosis from healthy controls. J Pain Res. 11:2981-2990. "This study attempted to utilize a novel predictive algorithm to identify a group of genes whose differential expression discriminated individuals with FMS diagnosis from healthy controls….The small-scale signature contained 57 genes whose expressions were highly discriminatory of the FMS diagnosis. The combination of these high discriminatory genes with FR higher than 1.45 provided a leave-one-out-cross-validation accuracy for the FMS diagnosis of 85.11%. The discriminatory genes were associated with 3 canonical pathways: hepatic stellate cell activation, oxidative phosphorylation, and airway pathology related to COPD. The discriminating genes, especially the 2 with the highest accuracy, are associated with mitochondrial function or oxidative phosphorylation and glutamate signaling."

Lukkahatai N, Walitt B, Espina A et al. 2015. Understanding the association of fatigue with other symptoms of fibromyalgia: Development of a cluster model. Arthritis Care Res (Hoboken). [May 27 Epub ahead of print.] "Two distinct clinical symptom sub-clusters emerged; sub-cluster 1 (78% of total subjects) defined by widespread pain, unrefreshed waking, and somatic symptoms and sub-cluster 2 (22% of total subjects) defined by fatigue and cognitive dysfunction with pain being a less severe and less widespread complaint….Overall, sub-cluster 1 had more intense symptoms than sub-cluster 2. FMS symptoms may be categorized into two clinical sub-clusters. These findings have implications for an illness whose diagnosis and management are symptom-dependent."

Lund E, Kendall SA, Janerot-Sjoberg B et al. 2003.  Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic exercise.  Scand J Rheumatol 32(3):138-145.  “Fibromyalgia patients seem to utilize less of the energy rich phosphorus metabolites at maximal work despite pH reduction.  They seemed to be less aerobically fit and reached the anaerobic threshold earlier than the controls.”

Lundberg M, Larsson M, Ostlund H et al. 2006.  Kinesiophobia among patients with musculoskeletal pain in primary healthcare.  J Rehabil Med. 38(1):37-43.  “…factors that seemed to be associated with kinesiophobia were interference, disability, pain severity, pain intensity, life control, affective distress, depressed mood and solicitous response.  The multiple logistic regression analysis showed no significant associations.”  “Kinesiophobia is a commonly seen factor among patients with musculoskeletal pain, which ought to be taken into consideration when designing and performing rehabilitation programs.”  [It is also important to understand that myofascial TrPs cause pain at the end of the range of motion, and it is logical for the patient to avoid range of motion when there is pain at the end of that range of motion.  The TrPs must be treated and the range of motion restored as much as possible so that the reason for the fear is removed.  Only then can remaining fear be considered as true kinesiophobia.  DJS]

Lunden LK, Jorum E. 2021. The challenge of recognizing severe pain and autonomic abnormalities for early diagnosis of CRPS. Scand J Pain. Apr 12. Online ahead of print. "All patients retrospectively reported intense pain…from the time of injury with a large discrepancy to previous medical records which only stated intense pain in 29.4% of patients with CRPS type 1 and 44.4% of patients with CRPS type 2 within the first four months. While the patients reported an early onset of autonomic dysfunction, present in 67.3 and 94.2% of the patients within one week and one month, respectively, reports of autonomic abnormalities within the first four months was far less (maximum in 51.7% of patients with CRPS type 1 and in 60% in CRPS 2). In 10 patients with CRPS type 1, no symptom nor sign of autonomic abnormalities was reported…. There is a large discrepancy between both self-reporting of intense, disproportionate pain, as well as symptoms of autonomic abnormalities from the time of injury, and documentation in previous medical records. Our findings suggest a lack of awareness of risk factors for the development of CRPS, such as early intense pain and autonomic abnormalities without recovery, contributing to delayed diagnosis. The present results suggest causes of delayed CRPS-diagnosis. An increased attention to early warning signs/risk factors may improve diagnosis of CRPS."

Luomala T, Pihlman M Heiskanen J et al. 2014. Case study: Could ultrasound and elastography visualize densified areas inside the deep fascia? J Bodyw Mov Ther. 18(3):462-468. "Many manual techniques describe palpable changes in the subcutaneous tissue. Many manual therapists have perceived palpable tissue stiffness and how it changes after treatment. No clear demonstration exists of the presence of specific alterations in the subcutaneous tissue and even less a visualization of their changes following manual therapy. This case study visualizes by ultrasound and elastography an alteration of the deep fascia in a 40-year-old male with subacute pain in the calf area. Ultrasound and elastography permits visualization of gliding, echogenicity and elasticity of deep fascia and their changes, after manual therapy (Fascial Manipulation(©)). This study suggests the possible use of the ultrasound and elastography to furnish a more objective picture of the "sensations" that are commonly reported by manual therapists, and which supports clinicians in the diagnosis of the myofascial pain."

Luoto, S., S. Taimela, H. Hurri and H. Alaranta.  1999.  Mechanisms explaining the association between low back trouble and deficits in information processing.  A controlled study with follow-up.  Spine 24(3):255-61.  

Luoto, S., H. Aalto, S. Taimela, H. Hurri, I. Pyykko and H. Alaranta.  1998.  One-footed and externally disturbed two-footed postural control in patients with chronic low back pain and healthy subjects.  A controlled study with follow-up.  Spine 23(19):2089-90.

Lupien, S.J., N. P. Nair, S. Briere, F. Maheu, M. T. Tu, M. Lemay, B. S. McEwen, M. J. Meaney. 1999. Increased cortisol levels and impaired cognition in human aging: implication for depression and dementia in later life. Rev Neurosci 10(2):17-39.

Lurie, M. , K. Caidahl , G. Johansson and B. Bake. 1990. Respiratory function in chronic primary fibromyalgia. Scand J Rehabil Med 22(3):151-5.

Lutz J, Schelling G, Stahl R et al.  Diffuse Tensor Imaging (DTI) danisotropic changes in the brain associated with chronic low back pain.  Radiological Society of North America Conference 29 Nov 2006.  Chicago IL.  (Conf. Nov 26-Dec 1)  “...chronification of lower back pain is associated with cortical and subcortical microstructural anisotropy changes .... these results argue for plastic changes of the cingulate gyrus, postcentral gyrus and the prefrontal cortex in chronic pain processing.”  There are microstructural changes in the brains of chronic pain patients, and DTI may explain and map some of what is happening in chronic pain.

Lynch ME, Campbell F. 2011. Cannabinoids for Treatment of Chronic Non-Cancer Pain; a Systematic Review of Randomized Trials. Br J Clin Pharmacol. [Mar 23 Epub ahead of print]. "Chronic non-cancer pain conditions included neuropathic pain, fibromyalgia, rheumatoid arthritis, and mixed chronic pain. Overall the quality of trials was excellent. Fifteen of the eighteen trials that met inclusion criteria demonstrated a significant analgesic effect of cannabinoid as compared to placebo, several reported significant improvements in sleep. There were no serious adverse effects. Adverse effects most commonly reported were generally well tolerated, mild to moderate in severity and led to withdrawal from the studies in only a few cases. Overall there is evidence that cannabinoids are safe and modestly effective in neuropathic pain with preliminary evidence of efficacy in fibromyalgia and rheumatoid arthritis. The context of the need for additional treatments for chronic pain is reviewed. Further large studies of longer duration examining specific cannabinoids in homogeneous populations are required."

Lyons KS, Jones KD, Bennett RM et al. 2013. Couple perceptions of fibromyalgia symptoms: The role of communication. Pain. [Jul 18 Epub ahead of print]. "The objectives of the current study were to 1) describe fibromyalgia patient-spouse incongruence regarding patient pain, fatigue, and physical function and 2) examine the associations of individual and interpersonal factors with patient-spouse incongruence. Two hundred four fibromyalgia patients and their co-residing partners rated the patient's symptoms and function. Multilevel modeling revealed that spouses, on average, rated patient fatigue significantly lower than patients. Couple incongruence was not significantly different from zero, on average, for pain severity, interference, or physical function. However, there was significant variability across couples in how they rated the severity of symptoms and function, and how much incongruence existed within couples. Controlling for individual factors, patient and spouse reports of communication problems were significantly associated with levels of couple incongruence regarding patient fatigue and physical function, albeit in opposing directions. Across couples, incongruence was high when patients rated communication problems as high; incongruence was low when spouses rated communication problems as high. An important within-couple interaction was found for pain interference suggesting couples who are similar on level of communication problems experience low incongruence; those with disparate ratings of communication problems experience high incongruence. Findings suggest the important roles of spouse response and the patient's perception of how well the couple is communicating. Couple-level interventions targeting communication or other interpersonal factors may help to decrease incongruence and lead to better patient outcomes."


Ma C, Wu S, Li G et al. 2010. Comparison of miniscalpel-needle release, acupuncture needling, and stretching exercise to trigger point in myofascial pain syndrome. Clin J Pain. 26(3):251-7.  “Myofascial pain syndrome (MPS) is one of the most common causes of chronic musculoskeletal pain. Several methods have been recommended for the inactivation of trigger points (TrPs). We carried out this study to investigate the effectiveness of miniscalpel-needle (MSN) release and acupuncture needling and self neck-stretching exercises on myofascial TrPs of the upper trapezius muscle.” This study found “the effectiveness of MSN release for MPS is superior to that of acupuncture needling treatment or self neck-stretching exercises alone. The MSN release is also safe, without severe side effects in treatment of MPS.” [The comparison may look good, but there are numerous techniques that may be at least as effective. Stretching alone is not an adequate treatment for TrPs in my opinion, and I would like to see this technique compared with the Travell and Simons’ technique (incorporating  proper positioning and full range of moti) of TrP injection with procaine or lidocaine, barrier release and spray and stretch. It is important to remember that no matter what the technique employed, control of perpetuating factors is critical to lasting treatment effect. DJS] 

Ma JJ, Ma TM, Wang L, et al. [Effect of moxibustion on the expression of microglia and brain-derived neurotrophic factor protein in the spinal cord of rats with myofascial pain syndrome.] Zhen Ci Yan Jiu. 2021 Sep 25;46(9):769-74. [Article in Chinese] "After treatment and compared with the model group, the TWL of the moxibustion group was significantly increased… in the moxibustion group. Rat's muscle fibers of the control group were uniform in thickness and arranged tightly and regularly. While in the model group, some fractures and connective structure tissue renewal, irregular arrangement, and inflammatory cell infiltration were seen. The morphology of muscle fibers in the moxibustion group was close to normal, and the arrangement was neat and orderly, with a small amount of inflammatory cell infiltration. Compared with the control group, the expression of OX-42 and BDNF in the spinal dorsal horn of rats in the model group was increased…. Following the treatment, and in comparison with the model group, the expression of OX-42 and BDNF of moxibustion group was down-regulated…. Conclusion: Moxibustion can significantly improve the injury of the medial femoral muscle and the TWL in MPS rats, which may be related to its effects in inhibiting the activation of spinal dorsal horn microglia and reducing the expression of BDNF. [The muscle fiber structure improvement may also be significant. DJS]

Ma L, Wang J, Li Y. 2015. Insulin resistance and cognitive dysfunction. Clin Chim Acta. 444:18-23. "Growing evidence supports the concept that insulin resistance is important in the pathogenesis of cognitive impairment and neurodegeneration. Insulin plays a profound role in cognitive function. Impaired insulin signaling in the advancement of cognitive dysfunction is relevant to the pathophysiologic mechanisms of cognitive impairment. In this paper we discuss the relationship between insulin resistance and cognitive impairment and review potential mechanisms of this disease process. Evidence, to date, suggests that brain insulin resistance is an independent risk factor for cognitive impairment." [This is one of many studies reminding us that cognitive dysfunction in FM patients may have multiple causes, such as this common co-existing condition. Those causes must be identified and treated, and only then can we truly be aware that what remains may be part of FM. DJS]

Ma W, Quirion R. 2014. Targeting cell surface trafficking of pain-facilitating receptors to treat chronic pain conditions. Expert Opin Ther Targets. [Feb 10 Epub ahead of print.] "Pain mediators stimulate forward surface trafficking of their own and/or other pain-facilitating receptors to amplify pain intensity and duration. Enhancing surface abundance of pain-facilitating receptors in nociceptors and dorsal horn neurons is an important mechanism underpinning chronic pain states. Targeting specific trafficking events of pain-facilitating receptors may open a novel therapeutic avenue to more efficiently treat chronic pain conditions."

Ma Y, Bu H, Jia JR et al. 2012. [Progress of research on acupuncture at trigger point for myofascial pain syndrome] 32(6):573-576. [Chinese]. This literature review covered acupuncture used on TrPs, taking into consideration both Traditional Chinese Medicine and modern clinical research applications. This review indicates that acupuncture on specific myofascial TrPs can significantly affect myofascial pain, but that results could be influenced by a number of variables including needle size and needling technique. Existing studies are insufficient and inconsistent, with inadequate use of clinical diagnostic standards. Good studies are needed.

Ma YT, Dong YL, Wang B, et al. Dry needling on latent and active myofascial trigger points versus oral diclofenac in patients with knee osteoarthritis: a randomized controlled trial. BMC Musculoskelet Disord. 2023 Jan 18;24(1):36. "Dry needling on latent and active MTrPs combined with stretching and oral diclofenac combined with stretching can effectively relieve pain, improve function, and restore knee ROM (range of motion) affected by KOA (knee osteoarthritis). However, the effects of dry needling and stretching are better and longer lasting than those of oral diclofenac and stretching for at least 6 months."

Ma YT, Li LH, Han Q, et al. 2020. Effects of trigger point dry needling on neuromuscular performance and pain of individuals affected by patellofemoral pain: A randomized controlled trial. J Pain Res. Jul 7;13:1677-1686. "Purpose: To investigate the effects of trigger point dry needling (TrP-DN) on exercise-induced patellofemoral pain syndrome (PFPS)…. Conclusion: TrP-DN at the quadriceps combined with stretch can reduce the pain, and improves the clinical symptoms and function, the VMO/VL (myoelectric amplitude of the vastus medialis oblique and vastus lateralis muscles) ratio, and the coordination of VMO and VL in patients with PFPS (patellofemoral pain syndrome)."

Mabry, R. L. and C. S. Mabry. 2000.  Allergic fungal sinusitis: the role of immunotherapy Otolaryngol Clin North Am 33(2):433-440.

MacDougall HG, Moore ST, Black RA et al. 2009.  On-road assessment of driving performance in bilateral vestibular-deficient patients.  Ann N Y Acad Sci. 1164:413-418.  “This has important implications for driver licensing, road-safety policy, and for the potential successful rehabilitation of vestibular patients.  Patients with unilateral vestibular dysfunction may have more difficulty driving than their bilateral counterparts.”  [This can be critical, as many patients with FM may have co-existing vestibular dysfunction. DJS]

Macerollo AA, Mack DO, Oza R et al. 2014. Academic family medicine physicians' confidence and comfort with opioid analgesic prescribing for patients with chronic nonmalignant pain. J Opioid Manag. 10(4):255-261. "This study was part of the Council of Academic Family Medicine (CAFM) Educational Research Alliance omnibus survey of active academic US family physicians….Most academic family physicians currently prescribed opioid analgesics to patients with chronic nonmalignant pain. There was a strong inverse relationship between confidence regarding opioid prescription and concern about negative consequences. Similarly, comfort level was tied to increased satisfaction with the overall process of opioid prescription."

Macfarlane GJ, Pathan E, Siebert S et al. 2019. AxSpA patients who also meet criteria for fibromyalgia: identifying distinct patient clusters using data from a UK national register (BSRBR-AS). BMC Rheumatol. May 20;3:19. "Around 1 in 8 patients with axial spondyloarthritis (axSpA) also meet criteria for fibromyalgia and such patients have considerable unmet need." This study found that patients with a high asSpA disease activity also had a high proportion of FM, although clusters of patients with less disease activity had a more moderate amount of FM. Thus, the FM pain component could be addressed without steroid or anti-inflammatory use. [This is logical, due to the CNS sensitization from pain. It would be useful to know what percentage of each cluster had myofascial trigger points contributing to the pain and CNS central sensitization. DJS]

Macgregor J, von Schweinitz DG. 2006.  Needle electromyographic activity of myofascial trigger points and control sites in equine cleidobrachialis muscle – an observational study.  Acupunct Med. 24(2):61-70.  “Equine myofascial trigger points can be identified and have similar objective signs and electrophysiological properties to those documented in human and rabbit skeletal muscle tissue.  The important differences from findings in human studies are that referred pain patterns and the reproduction of pain profile cannot be determined in animals."

Maddox EK, Massoni SC, Hoffart CM, et al. Dietary effects on pain symptoms in patients with fibromyalgia syndrome: Systematic review and future directions. Nutrients. 2023 Jan 31;15(3):716. "Fibromyalgia syndrome (FMS) is recognized for its difficulty to diagnose and its subjective symptomatology. There is neither a known cure nor a recommended therapeutic diet to aid in the multidisciplinary treatment…. Given the small sample size and short intervention duration of the included studies, limited evidence currently exists to recommend any specific diet to patients with FMS."

Madeleine P, Vangsgaard S, Hviid Andersen J et al. 2013. Computer work and self-reported variables on anthropometrics, computer usage, work ability, productivity, pain and physical activity. BMC Musculoskel Disord 14:226. "The differences in pain characteristics, i.e., higher intensity, longer duration and more pain locations as well as poorer work ability reported by women workers relate to their higher risk of contracting WMSD (work-related musculoskeletal disorders). Overall, this investigation confirmed the complex interplay between anthropometrics, work ability, productivity, and pain perception among computer workers."

Maekawa K, Clark GT, Kuboki T. 2002.  Intramuscular hypoperfusion, adrenergic receptors, and chronic muscular pain. Aug 3(4):251-260.  This review focuses on the sympathetic connection between fibromyalgia and myofascial pain.  The authors state “What cannot be done at this time and is needed in the future is to compare and contrast to what degree the regional muscle pain disorder (myofascial) is similar or different from the more generalized disorder (fibromyalgia.)”  I agree that it must be done.  I also think that it can be.

Maes M, Twisk FN, Johnson C. 2012. Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), and Chronic Fatigue (CF) are distinguished accurately: Results of supervised learning techniques applied on clinical and inflammatory data. Psychiatry Res. [Apr 20 Epub ahead of print]. "There is much debate on the diagnostic classification of Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS) and chronic fatigue (CF). Post-exertional malaise (PEM) is stressed as a key feature. This study examines whether CF and CFS, with and without PEM, are distinct diagnostic categories. Fukuda's criteria were used to diagnose 144 patients with chronic fatigue and identify patients with CFS and CF, i.e. those not fulfilling the Fukuda's criteria. PEM was rated by means of a scale with defined scale steps between 0 and 6. CFS patients were divided into those with PEM lasting more than 24h (labeled: ME) and without PEM (labeled: CFS). The 12-item Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale was used to measure severity of illness. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α , and lysozyme, and serum neopterin were employed as external validating criteria. Using fatigue, a subjective feeling of infection and PEM we found that ME, CFS, and CF were distinct categories. Patients with ME had significantly higher scores on concentration difficulties and a subjective experience of infection, and higher levels of IL-1, TNFα, and neopterin than patients with CFS. These biomarkers were significantly higher in ME and CFS than in CF patients. PEM loaded highly on the first two factors subtracted from the data set, i.e. "malaise-sickness" and "malaise-hyperalgesia". Fukuda's criteria are adequate to make a distinction between ME/CFS and CF, but ME/CFS patients should be subdivided into ME (with PEM) and CFS (without PEM)."

Maeshima E, Furukawa K. 2012. A case of fibromyalgia syndrome with anaphylaxis induced by intradermal injection of purified protein derivative. Mod Rheumatol. [Jun 10 Epub ahead of print]. "When a 36-year-old woman with fibromyalgia syndrome (FMS) underwent the tuberculin test, urticaria developed on her trunk at 30 min after intradermal injection of purified protein derivative. Although the urticaria resolved, fever, facial edema, and generalized urticaria occurred after 8 h. A patient with FMS who developed a systemic allergic reaction after an intradermal skin test has not been reported. We should pay attention to anaphylactic reactions after intradermal injection in patients with FMS."

Magerl W, Thalacker E, Vogel S et al. 2021. Tenderness of the skin after chemical stimulation of underlying temporal and thoracolumbar fasciae reveals somatosensory crosstalk between superficial and deep tissues. Life (Basel). Apr 21;11(5):370. "The experiments demonstrated that fascia stimulation at a sufficient stimulus intensity elicited significant across-tissue facilitation to pinprick stimulation (referred hyperalgesia), a hallmark sign of nociceptive central sensitization."

Maggi RG, Mozayeni BR, Pultorak EL et al. 2012. Bartonella spp. Bacteremia and Rheumatic Symptoms in Patients from Lyme Disease-endemic Region. Emerg Infect Dis. 18(5):783-791. "Bartonella spp. infection has been reported in association with an expanding spectrum of symptoms and lesions. Among 296 patients examined by a rheumatologist, prevalence of antibodies against Bartonella henselae, B. koehlerae, or B. vinsonii subsp. berkhoffii (185 [62%]) and Bartonella spp. bacteremia (122 [41.1%]) was high. Conditions diagnosed before referral included Lyme disease (46.6%), arthralgia/arthritis (20.6%), chronic fatigue (19.6%), and fibromyalgia (6.1%). B. henselae bacteremia was significantly associated with prior referral to a neurologist, most often for blurred vision, subcortical neurologic deficits, or numbness in the extremities, whereas B. koehlerae bacteremia was associated with examination by an infectious disease physician. This cross-sectional study cannot establish a causal link between Bartonella spp. infection and the high frequency of neurologic symptoms, myalgia, joint pain, or progressive arthropathy in this population; however, the contribution of Bartonella spp. infection, if any, to these symptoms should be systematically investigated."

Magnan EM, Tancredi DJ, Xing G, et al. Association between opioid tapering and subsequent health care use, medication adherence, and chronic condition control. JAMA Netw Open. 2023 Feb 1;6(2):e2255101."In this cohort study of patients prescribed LTOT (long-term opioid therapy), opioid tapering was associated with more emergency department visits and hospitalizations, fewer primary care visits, and reduced antihypertensive and antidiabetic medication adherence. These outcomes may represent unintended negative consequences of opioid tapering for policy makers and clinicians to consider."

Magrey MN, Antonelli M, James N et al. 2013. High frequency of fibromyalgia in patients with psoriatic arthritis: a pilot study. Arthritis. [Feb 14 Epub ahead of print]. "FMS-associated pain and fatigue are significantly more frequent in patients with PsA compared to controls."

Magtanong GG, Spence AR, Czuzoj-Shulman N etal. 2017. Maternal and neonatal outcomes among pregnant women with fibromyalgia: a population-based study of 12 million births. J Matern Fetal Neonatal Med. 27:1-7. "Fibromyalgia (FM) is a rheumatologic disorder marked by chronic, widespread pain and associated comorbid conditions. The purpose of our study was to evaluate the effect of FM on maternal and neonatal outcomes…. Of 12,584,918 births during the 15-year study period, 7758 were to women with FM with rates increasing over the study period. Women with FM were more commonly older in age, overweight or obese, and users of alcohol, tobacco, and illicit drugs. They were more likely to experience anxiety, depression, and bipolar disorder. Women with FM were at greater risk of gestational diabetes, preterm premature rupture of membranes, and placental abruption. Women with FM more commonly had cesarean deliveries… and births complicated by venous thromboembolism….. Infants of women with FM were more likely to be premature…. and have intrauterine growth restriction …. The prevalence of FM in pregnancy is rising in the US. FM is a high-risk pregnancy condition associated with adverse maternal and newborn outcomes."

Mahakkanukrauh P, Surin P, Vaidhayakam P. 2005. Anatomical study of the pudendal nerve adjacent to the sacrospinous ligament. Clin Anat 18(3):200-205. The pudendal nerve can be entrapped in a variety of places. "Eight of fifteen rectal nerves pierced through the sacrospinous ligament, perhaps making it prone for entrapment." [Deep ligaments may be the site of TrP nerve entrapment. DJS]

Maher, J. 2000. Report investigating the importance of head restraint positioning in reducing neck injury in rear impact. Accid Anal Prev 32(2):299-305.

Maher RM, Hayes DM, Shinohara, M. 2013. Quantification of dry needling and posture effects on myofascial trigger points using ultrasound shear-wave elastography. Arch Phys Med Rehabil. 94(11):2146-2150. "The shear modulus measured with ultrasound SWE (shear-wave elastography) reduced after DN (dry needling) and in the prone position compared with sitting, in agreement with reductions in palpable stiffness. These findings suggest that DN and posture have significant effects on the shear modulus of MTrPs, and that shear modulus measurement with ultrasound SWE may be sensitive enough to detect these effects."

Mahowald ML, Singh JA, Majeski P. 2005.  Opioid use by patients in an orthopedics spine clinic.  Arthritis Rheum. 52(1):312-321.  “This study provides clinical evidence to support and protect physicians treating patients with chronic musculoskeletal diseases, who may be reluctant to prescribe opioids because of possible sanctions from regulatory agencies.  More important, it will benefit patients by permitting them to receive these effective, safe medications.

Maia MM, Gualano B, Sa-Pinto AL et al. 2016. Juvenile fibromyalgia syndrome: Blunted heart rate response and cardiac autonomic dysfunction at diagnosis. Semin Arthritis Rheum. [Jul 16 Epub ahead of print.] This study identified chronotropic incompetence and delayed HR (heart-rate) recovery in JFM patients, indicating autonomic dysfunction. Aerobic exercise training should be considered in all JFM patients and may improve cardiac autonomic impairment, thus reducing cardiovascular risk.

Maigne JY, Doursounian L. 1997.  Entrapment neuropathy of the medial superior cluneal nerve.  Nineteen cases surgically treated, with a minimum of 2 years’ follow-up.  Spine 22(10):1156-1159. “Nineteen patients suffering from unilateral low back pain projecting in the territory of the medial superior cluneal nerve, with a trigger point at the posterior iliac crest and with a positive block test at this level, underwent surgery.  Results: Results were excellent in 13 cases (7 of which had suffered from severe compression), and unsatisfactory in 6 cases (including 4 cases in whom no compression could be demonstrated).  Conclusion: Entrapment neuropathy of the medial superior cluneal nerve is a rare and easily treatable cause of unilateral low back pain.”

Maigne JY, Maigne R. 1991.  Trigger point of the posterior iliac crest: painful iliolumbar ligament insertion or cutaneous dorsal ramus pain?  An anatomic study.  Arch Phys Med Rehabil. 72(10):734-737.  “A trigger point is frequently found over the iliac crest at 7 to 8 cm from the midline in low-back-pain syndromes.”  “The iliac insertion of the iliolumbar ligament is inaccessible to palpation, being shielded by the iliac crest.”  “The authors conclude that the trigger point sometimes localized over the iliac crest at 7 cm from the midline likely corresponds to elicited pain from a cutaneous dorsal ramus originating from the thoracolumbar junction rather than from the iliac insertion of the iliolumbar ligament.”

Maigne, R. 1997. Pain syndromes of the thoracolumbar junction. Myofascial Pain–Update in Diagnosis and Treatment. Phys Med Rehab Clin North Am 8(1):87-100.

Majidi L, Kargar Z, Alaei B, et al. Comparison of the effectiveness of exercise therapy and electroacupuncture in patients with forward head abnormalities and myofascial pain syndrome: A randomized clinical trial. Med J Islam Repub Iran. 2023 Apr 8;37:34. Overall, the results of this study showed that both exercise therapy and electroacupuncture significantly improved patients' posture, reduced pain intensity, and increased quality of life in FHP (Forward Head Posture) patients with MPS; But exercise therapy was more effective in improving FHP angles and electroacupuncture was more successful in reducing patients' pain intensity."

Majlesi J, Unalan H. 2004.  High-power pain threshold ultrasound technique in the treatment of active myofascial trigger points: a randomized, double blind, case-control study.  Arch Phys Med Rehabil 85:833-836.  This study found that high-power ultrasound, using a specific technique, can quickly find and treat TrPs.  [There was no significant change in range of motion, which may indicate that the TrPs were simply rendered latent, but the pain levels were reduced significantly.  This therapy shows promise, although there are some areas in which it cannot be utilized.  DJS]

Majlesi J, uNalan H.  2004.  High-power pain threshold ultrasound technique in the treatment of active myofascial trigger points:  A randomized, double-blind, case-control study.  Arch Phys Med Rehabil. 85(5):833-836.  This technique was more effective than conventional ultrasound.

Malanga GA, Cruz Colon EJ. 2010. Myofascial low back pain: a review. Phys Med Rehabil Clin N Am. 21(4):711-724. Myofascia pain is common, found in up to 95% of chronic pain patients. TrPs can occur in muscle, fascia or tendons, and are often caused by muscle imbalance. [Often they are the cause of muscle imbalance DJS] There is a wide variety of treatment options, but steroids should not be used for TrP injection therapy.

Malanga GA, Gwynn MW, Smith R et al. 2002.  Tizanidine is effective in the treatment of myofascial pain syndrome.  Pain Physician 5(4):422-432.

Malatji BG, Mason S, Mienie LJ et al. 2019. The GC-MS metabolomics signature in patients with fibromyalgia syndrome directs to dysbiosis as an aspect contributing factor of FMS pathophysiology. Metabolomics. Mar 27;15(4):54. This study was done on the urinary metabolic products of 18 female fibromyalgia patients, with controls from their first-generation healthy family members, and a separate group of age related healthy individuals. "Quantitative analysis revealed the presence of 196 metabolites. Unsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, which could be related to 14 significantly increased metabolites. These metabolites are associated with energy metabolism, digestion and metabolism of carbohydrates and other host and gut metabolites.... Overall, urinary metabolite profiles in the FMS patients suggest: (1) energy utilization is a central aspect of this pain disorder, (2) dysbiosis seems to prevail in FMS patients, indicated by disrupted microbiota metabolites, supporting the model that microbiota may alter brain function through the gut-brain axis, with the gut being a gateway to generalized pain, and (3) screening of urine from FMS is an avenue to explore for adding non-invasive clinical information for diagnosis and treatment of FMS."

Malatji BG, Meyer H, Mason S et al. 2017. A diagnostic biomarker profile for fibromyalgia syndrome based on an NMR metabolomics study of selected patients and controls. BMC Neurol. 17(1):88. "Unsupervised and supervised multivariate analyses distinguished all three control groups and the FMS patients, and significant increases in metabolites related to the gut microbiome (hippuric, succinic and lactic acids) were observed. We have developed an algorithm for the diagnosis of FMS consisting of three metabolites - succinic acid, taurine and creatine - that have a good level of diagnostic accuracy (Receiver Operating Characteristic (ROC) analysis - area under the curve 90%) and on the pain and fatigue symptoms for the selected FMS patient group…Our data and comparative analyses indicated an altered metabolic profile of patients with FMS, analytically detectable within their urine. Validation studies may substantiate urinary metabolites to supplement information from medical assessment, tender-point measurements and FIQR questionnaires for an improved objective diagnosis of FMS." Free Article

Malfliet A, Kregel J, Meeus M et al. 2018. Patients with chronic spinal pain benefit from pain neuroscience education regardless the self-reported signs of central sensitization: Secondary analysis of a randomized controlled multicenter trial. PM R. May 9. [Epub ahead of print] "Pain neuroscience education is effective in chronic pain management. Central sensitization (ie, generalized hypersensitivity) is often explained as the underlying mechanism for chronic pain, because of its clinical relevance and influence on pain severity, prognosis, and treatment outcome....Pain neuroscience education is useful in all patients with chronic spinal pain as it improves kinesiophobia and the perceived negative consequences and cyclicity of the illness regardless the self-reported signs of central sensitization. Regarding pain catastrophizing, pain neuroscience education is more effective in patients with high self-reported symptoms of central sensitization."

Malhotra D, Saxena AK, Dar A+SA, et al. 2012. Evaluation of cytokine levels in fibromyalgia syndrome patients and its relationship to the severity of chronic pain. J Musculoskel Pain. 20(3):164-169. [Elevated levels of cytokines and other pro-inflammatory substances have been implicated in fibromyalgia. This study indicates that Interleukin-6, a pro-inflammatory substance, may be active in the process of increased pain in fibromyalgia. This indicates a possible role of inflammation in fibromyalgia. While not an inflammatory disease per se, IL-6, a pro-inflammatory cytokine, does affect glial cells as shown in the research of Dr. Linda Watkins and her team. [see Wieseler-Frank J, Maier SF, Watkins LR. 2005. Immune-to-brain communication dynamically modulates pain: physiological and pathological consequences. Brain Behav Immun. 19(2):104-111.] Pro-inflammatory cytokines can cause diffuse muscle aches, fatigue, hyperalgesia, depressed mood, and may other symptoms associated with FM. The authors urge large multicenter investigations, and explain that the exact role of inflammation in FM is not fully established. We hope for more research to follow up this excellent article. DJS]

Malin K, Littlejohn GO. 2012. Personality and fibromyalgia syndrome. Open Rheumatol J. 6:273-285. "No specific fibromyalgia personality is defined but it is proposed that personality is an important filter that modulates a person's response to psychological stressors. Certain personalities may facilitate translation of these stressors to physiological responses driving the fibromyalgia mechanism."

Malin K, Littlejohn GO. 2012. Psychological control is a key modulator of fibromyalgia symptoms and comorbidities. J Pain Res. 5:463-471. "FM patients use significantly different control styles compared with healthy individuals. Levels and type of psychological control buffer mood, stress, fatigue, and pain in FM. Control appears to be an important "up-stream" process in FM mechanisms and is amenable to intervention."

Mallorquí-Bague N, Bulbena A, Roe-Vellve N et al. 2015. Emotion processing in joint hypermobility: A potential link to the neural bases of anxiety and related somatic symptoms in collagen anomalies. Eur Psychiatry. [Feb 12 Epub ahead of print.] This article from Spain found: "Joint hypermobility syndrome (JHS) has repeatedly been associated with anxiety and anxiety disorders, fibromyalgia, irritable bowel syndrome and temporomandibular joint disorder. However, the neural underpinnings of these associations still remain unclear. This study explored brain responses to facial visual stimuli with emotional cues using fMRI techniques in general population with different ranges of hypermobility….Hypermobility scores are associated with trait anxiety and higher brain responses to emotional faces in emotion processing brain areas (including hippocampus) described to be linked to anxiety and somatic symptoms. These findings increase our understanding of emotion processing in people bearing this heritable variant of collagen and the mechanisms through which vulnerability to anxiety and somatic symptoms arise in this population." [This is an article in a psychiatry journal; the authors looked at this condition through that lens. DJS]

Malmberg, A. B., C. Chen, S. Tonegawa and A.I. Basbaum. 1997. Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma. Science 278(5336):279-83.

Mamelak M. 2000.  The motor vehicle collision injury syndrome.  Neuropsychiatry Neuropsychol Behav Neurol. 13(2):125-135.  “Occupants of motor vehicles involved in a collision often develop a disabling syndrome consisting of head, neck and back pain; impaired short-term memory and concentration; fatigue and a loss of stamina; poor balance; and a change in personality.  Injury victims experience a loss of motivation, emotional lability, and a decrease in libido.  It is hypothesized that the collision impact produces an inertial strain injury to the anterior regions of the brain which depresses the functions of the frontotemporal lobes, at the same time, sensitizing somatosensory neural afferent systems.  Damage to the orbital surfaces of the frontotemporal lobes, in particular, impairs the gating mechanisms that normally limit sensory input to the brain and further promotes central sensitization.  Early intervention to arrest the injury-induced metabolic cascade, and treatment with agents that activate cerebral metabolism may mitigate the symptoms of this injury syndrome.”

Manchikanti L. 2004.  The growth of interventional pain management in the new millennium: a critical analysis of utilization in the Medicare population.  Pain Physician. 7(4):465-482.  “It is estimated that among Medicare recipients, the frequency of interventional procedures, which includes epidural, spinal neurolysis, and adhesiolysis procedures; facet joint interventions and sacroiliac joint blocks; and other types of nerve blocks excluding continuous epidurals, implantables, disc procedures, intraarticular injections, trigger point and ligament injections, had increased by 95% from 1998 to 2003.”  [The “bottom line” seems to be the new criteria for medical management.  Certainly, wiser decisions must be made in the field of chronic pain.  This can best happen by education in interactive diagnoses rather than reliance on differential diagnosis, and the inclusion of myofascial pain and chronic pain management in all medical fields. DJS]

Manchikanti L, Abdi S, Atluri S et al. 2012. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance. Pain Physician. 15(3 Suppl):S67-116. "Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. EVIDENCE: good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. (EVIDENCE: limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. (EVIDENCE: good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. (EVIDENCE: good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. (EVIDENCE: good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. (EVIDENCE: good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation may assist non-pain physicians if high-dose opioid therapy is utilized. (EVIDENCE: fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. (EVIDENCE: good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (EVIDENCE: good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. (EVIDENCE: fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. (EVIDENCE: fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. (EVIDENCE: fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. (EVIDENCE: fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. (EVIDENCE: fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. (EVIDENCE: good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. (EVIDENCE: limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. (EVIDENCE: fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. (EVIDENCE: fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. (EVIDENCE: good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. (EVIDENCE: fair)." DISCLAIMER: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care." Free Article

Mandal, A. C. 1984. The correct height of school furniture. Physiotherapy 70(2):48-53.

Mangnus TJP, Dirckx M, Huygen FJPM. Different types of pain in complex regional pain syndrome require a personalized treatment strategy. J Pain Res. 2023 Dec 27:16:4379-4391. In this review, the types of pain recognized by the IASP-nociceptive, neuropathic, and nociplastic pain-will be discussed as possible subgroups for CRPS…. Over the course of the syndrome, patients with CRPS probably experience more than one distinct pain type. Therefore, pain specialists should be alert to not only adjust their treatment if underlying pathophysiologic mechanisms tend to change but also to personalize the treatment of the associated type of pain in the CRPS patient.

Mani N, Jun HW, Beach JW et al. 2003.  Solubility of guaifenesin in the presence of common pharmaceutical additives.  Pharm Dev Technol 8(4):385-96.  Common additives can change the aqueous solubility of guaifenesin.  This indicates that all compounds of guaifenesin may not have equal solubility and possibly may not be equivalent in bioavailability as well. 

Mannerkorpi K, Gard G. 2012. Hinders for continued work among persons with fibromyalgia. BMC Musculoskelet Disord. 13(1):96. "Work disability is common among women with fibromyalgia (FM). The aim of the study was to investigate what health problems and work-related difficulties lead to hinders for continued work among women with FM.....Health problems and work-related demands were identified. Limited physical capacity, increased stress and an increased need of rest were the major health problems, while physical, psychosocial and work organizational demands were the main work-related problems. Personal factors and factors related to family influenced the strategies used to manage the imbalance between the health problems and work-related demands.....Limited physical capacity and an increased need of rest made it difficult for these women to manage the physical, psychosocial and organizational work demands. Adjustment of the work tasks and work environment were the main factors influencing whether the women with FM could work or not."

Mannerkorpi K, Nordeman L, Ericsson A et al. 2009.  Pool exercise for patients with fibromyalgia or chronic widespread pain: a randomized controlled trial and subgroup analyses.  J Rehabil Med. 41(9):751-760.  “The exercise-education program showed significant, but small, improvement in health status in patients with fibromyalgia and chronic widespread pain, compared with education only.  Patients with milder symptoms improved most with this treatment.”

Mannerkorpi K., Ahlmen M., Ekdahl C. 2002.  Six- and 24-month follow-up of pool exercise therapy and education for patients with fibromyalgia.  Scand J Rheumatol 31(5):306-10. This study showed lasting improvements even 24 months after the completion of the therapy.  [It would be valuable to evaluate the use of pool therapy in patients with both fibromyalgia and chronic myofascial pain, and to specify which pool temperatures are most effective. DJS]

Mansour M, Ehrenberg S, Mahroum N, et al. 2024. The existence of a bidirectional link between ischemic heart disease and fibromyalgia. Coron Artery Dis. 2024 Mar 1;35(2):99-104. "Our data suggest a bidirectional link between FM and IHD (ischemic heart disease) even after the adjustment for conventional cardiovascular risk factors. These findings should be considered when treating patients with either FM or IHD, and their routine interactional screening may be of clinical importance."

Mantyselka P, Kumpusalo E, Ahonen R et al. 2001. Patients' versus general practitioners' assessments of pain intensity for primary care patients with non-cancer pain. Br J Gen Pract 51(473):995-997. "GPs tended to estimate their patients' pain intensity as clinically significantly lower than the patients themselves, particularly in chronic and severe pain."

Mantyselka PT, Kumpusalo EA, Ahonen RS et al. 2002. Direct and indirect costs of managing patients with musculoskeletal pain—challenge for health care. Eur J Pain 6(2):141-148. "Musculoskeletal pain is an outstanding symptom among the patients of primary health care. Musculoskeletal pain is not just a frequent complaint but also has extensive economic consequences for society."

Mao J, Gold MS, Backonja MM. 2010. Combination Drug Therapy for Chronic Pain: A Call for More Clinical Studies. J Pain. [Sep 16 Epub ahead of print]. "Chronic pain is a debilitating clinical condition associated with a variety of disease entities including diabetic neuropathy, postherpetic neuralgia, low back pathology, fibromyalgia, and neurological disorders. For many general practitioners and specialists, managing chronic pain has become a daunting challenge. As a modality of multidisciplinary chronic pain management, medications are often prescribed in combinations, an approach referred to as combination drug therapy (CDT). However, many medications for pain therapy, including antidepressants and opioid analgesics, have significant side effects that can compound when used in combination and impact the effectiveness of CDT. To date, clinical practice of CDT for chronic pain has been based largely on clinical experiences. In this article, we will focus on (1) the scientific basis and rationales for CDT, (2) current clinical data on CDT, and (3) the need for more clinical studies to establish a framework for the use of CDT. ....More preclinical, clinical, and translational studies are needed to improve the efficacy of combination drug therapy that is an integral part of a comprehensive approach to the management of chronic pain." [Many of the conditions mentioned have as a common pain generator myofascial trigger points. Many TrP therapies are themselves painful. It is greatly to be hoped that, as we uncover the mechanisms of TrPs, useful medication regimens for chronic myofascial pain will be developed. DJS]

Maquet D, Croisier JL, Renard C, Crielaard JM. 2002. Muscle performance in patients with fibromyalgia. Joint Bone Spine 69(3):293-9. "This study of the three pathways supplying energy to muscle confirms that muscle function is globally impaired in FMS patients.  The results suggest that the impairment predominated on aerobic processes."

Marcus DA. 2006.  A review of perinatal acute pain: treating perinatal pain to reduce adult chronic pain.  J Headache Pain 7(1):3-8.  “Over the last decade, studies have suggested that exposure to repeated painful procedures during the early perinatal period results in profound changes in sensitivity of nociceptive pathways.  Both animal and human studies show that early pain experiences increase pain responses beyond the period of infancy.  These data suggest a need to increase implementation of guidelines for minimizing pain exposures during infancy.”

Marcus, D. A. 2000. Treatment of nonmalignant chronic pain. Am Fam Physician 61(5):1331-8, 1345-6.

Marcus DA, Bernstein CD, Constantin JM et al. 2012. Impact of Animal-Assisted Therapy for Outpatients with Fibromyalgia. Pain Med. [Nov 21 Epub ahead of print]. "Animal-assisted therapy using dogs trained to be calm and provide comfort to strangers has been used as a complementary therapy for a range of medical conditions. This study was designed to evaluate the effects of brief therapy dog visits for fibromyalgia patients attending a tertiary outpatient pain management facility compared with time spent in a waiting room. Brief therapy dog visits may provide a valuable complementary therapy for fibromyalgia outpatients."

Marcus DA, Richards KL, Chambers JF et al. 2012. Fibromyalgia Family and Relationship Impact Exploratory Survey. Musculoskeletal Care. [Nov 21 Epub ahead of print]. Fibromyalgia is frequently associated with impairments in activities of daily living and work disability. Limited data have investigated the impact of fibromyalgia on relationships with family and friends.....Half of participants endorsed that fibromyalgia had mildly to moderately damaged relationship(s) with their spouse(s)/partner(s) or contributed to a break-up with a spouse or partner. Half of participants scored as not being satisfied with their current spouse/partner relationship, with satisfaction negatively affected by the presence of mood disturbance symptoms and higher fibromyalgia severity. Relationships with children and close friends were also negatively impacted for a substantial minority of participants....In addition to physical impairments that are well documented among individuals with fibromyalgia, fibromyalgia can result in a substantial negative impact on important relationships with family and close friends.

Marcus NJ, Shrikhande AA, McCarberg B et al. 2013. A preliminary study to determine if a muscle pain protocol can produce long-term relief in chronic back pain patients. Pain Med. [May 20 Epub ahead of print]. This study was done on patients with neuraxal low back pain, testing before and after invasive treatments. They used an electrical device to find possible sources of pain, rather than palpation. The study found that identifying and treating painful muscles produced significantly lasting reductions in pain as well as function improvement. Some patients cancelled their surgeries. Others had failed back surgery, failed epidural steroid injections, and/or TrP injections. With treatment of muscle and tendon pain generator, their pain was significantly relieved using this muscle protocol. Both the muscles and their tendon attachments were critical pain generators.

Margalef R, Sisquella M, Bosque M et al. 2018. Experimental myofascial trigger point creation in rodents. J Appl Physiol (1985). [Oct 11 Epub ahead of print] "Myofascial pain syndrome is one of the most common forms of muscle pain. In this syndrome pain is originated by the so-called trigger points, which consists of a set of palpable contraction knots in the muscle. It has been proposed that a high spontaneous neurotransmission may be involved in the generation of these contraction knots. To confirm this hypothesis, we exposed mouse muscles to an anticholinesterasic agent to increase the neurotransmision in the synaptic cleft in two different conditions, in vivo and ex vivo experiments. Using intracellular recordings a sharp increase in the spontaneous neurotransmission in the levator auris longus muscle and a lower increase in the diaphragm muscle could be seen. Likewise electromyography recordings reveal an elevated endplate noise in gastrocnemius muscle of treated animals. These changes are associated with structural changes such as abundant neuromuscular contracted zones observed by rhodaminated α-bungarotoxin and the presence of abundant glycosaminoglycan's around the contraction knots evidenced by Alcian PAS staining. In a second set of experiments we aimed at demonstrating that the increases in the neurotransmission reproduced most of the clinical signs associated to a trigger point. We exposed rats to the anticholinesterase agent neostigmine and 30 min. after we observed the presence of palpable taut bands, the echocardiographic presence of contraction knots and local twitch responses upon needle stimulation. In summary, we demonstrated that increased neurotransmission induced trigger points in both rats and mice and we evidenced glycosaminoglycan's around the contraction zones as a novel hallmark of this pathology."

Marin, P., and S. Arver. 1998. Androgens and abdominal obesity. Ballieres Clin Endocrinol Metab 12(3):441-51.

Markotic F, Cerni Obrdalj E, Zalihic A et al. 2013. Adherence to pharmacological treatment of chronic nonmalignant pain in individuals aged 65 and older. Pain Med. [Jan 31 Epub ahead of print]. "According to their own statements, 57% of the patients were nonadherent, while 84% exhibited some form of nonadherence …The most common deviation from the prescribed therapy was self-adjustment of the dose and medical regimen based on the severity of pain. Polymedication correlated positively with nonadherence. Nonsteroidal anti-inflammatory drugs were the most frequently prescribed medications. The majority of the participants (59%) believed that higher pain intensity indicates progression of the disease, and half of the participants believed that one can easily become addicted to pain medications. Nonadherence was associated with patient attitudes about addiction to analgesics and ability of analgesics to control pain….High pain intensity and nonadherence found in this study suggest that physicians should monitor older patients with chronic nonmalignant pain more closely and pay more attention to patients' beliefs regarding analgesics to ensure better adherence to pharmacological therapy." [Many patients have incorrect understanding of medications, and may fail to use sufficient medication to control their symptoms due to fear of addiction DJS]

Markozannes G, Aretouli E, Rintou E et al. 2017. An umbrella review of the literature on the effectiveness of psychological interventions for pain reduction. BMC Psychol. 5(1):31. "Of the 141 associations based on only randomized controlled trials, none presented strong or highly suggestive evidence by satisfying all the aforementioned criteria. The effect of psychological interventions on reducing cancer pain severity, pain in patients with arthritis, osteoarthritis, rheumatoid arthritis, breast cancer, fibromyalgia, irritable bowel syndrome, self-reported needle-related pain in children/adolescents or with chronic musculoskeletal pain, chronic non-headache pain and chronic pain in general were supported by suggestive evidence….The present findings reveal the lack of strong supporting empirical evidence for the effectiveness of psychological treatments for pain management and highlight the need to further evaluate the established approach of psychological interventions to ameliorate pain."

Marks DM, Newhouse A. 2015. Durability of benefit from repeated intravenous lidocaine infusions in fibromyalgia patients: A Case Series and Literature Review. Prim Care Companion CNS Disord. 17(5). "Fibromyalgia is a painful disorder with no curative treatments, and available medications typically provide partial relief of pain. Reported here is the effective use of serial intravenous lidocaine infusions for the chronic management of 3 patients with fibromyalgia. The details of the infusion procedure are described, and relevant literature is reviewed. Lidocaine infusions should be considered in fibromyalgia patients who are refractory to other treatments, and a positive response to 1 infusion may justify repeated infusions for chronic management." Free PMC Article

Markus J, Sibbing IC, Ket JCF et al. 2020. Treatment strategies for anterior cutaneous nerve entrapment syndrome in children: A systematic review. J Pediatr Surg. May 16. [Epub ahead of print] "Anterior cutaneous nerve entrapment syndrome (ACNES) is a frequently overlooked cause of chronic abdominal pain in children…. Six studies, involving 224 patients, were included with an overall quality reported to be between fair and poor. Treatment success of local injections with an anesthetic agent into the trigger point ranged from 38% to 87% with a follow-up ranging from 4 weeks to 39 months. In addition, treatment success of anterior neurectomy ranged from 86% to 100%, with a follow-up duration ranging from 4 weeks to 36 months…. A step-up treatment strategy should be applied when treating pediatric patients with ACNES. This strategy starts with an injection with a local anesthetic agent, reserving surgery (anterior neurectomy) as a viable option in case of persistent pain." [One must also identify and control all perpetuating factors before considering surgery. DJS]

Marmann P, Wiatrek W. Observational study to assesses the efficacy and safety of microcurrent therapy with a portable device in patients suffering from chronic back pain, skeletal system pain, fibromyalgia, migraine or depression. Med Devices (Auckl). 2023 Dec 7:16:261-280. Microcurrent therapy has been demonstrated to be efficient and safe under real-world conditions for the treatment of each of the conditions for which the device is certified.

Marqulis RK, Borrero M. 2010. Distant surgery scar points and fascial adhesions perpetuate pectoralis minor trigger points in two cases of severe chronic palmar pain. International Myopain Society Eighth Clinical Meeting Oct 3-7, 2010. Toledo, Spain. Abstract No. 91. "In these cases, the distant scar points and fascial adhesions on acupuncture channels acted as trigger point perpetuating factors: when these factors were successfully treated, the trigger points resolved and did not return. This is believed to be the first report of scar points and fascial adhesions as distant trigger point perpetuating factors." [Actually, previous significant research has been published on the topic of scars and TrPs by both Dr. Karl Lewit and Dr.Alena Kobesova. DJS]

Marr NC, Van Liew C, Carovich TF et al. 2020. The effects of racial/ethnic minority status on sleep, mood disturbance, and depression in people with fibromyalgia. Psychol Res Behav Manag. 13:343-353. "Racial/ethnic minorities reported significantly greater levels of sleep disturbance, significantly greater levels of mood disturbance, and had significantly greater levels of depression than White participants. However, racial/ethnic minorities had significantly greater reductions in mood disturbance over the one-year period than White participants."

Marshall R, Paul L, McFadyen AK et al. 2010. Pain characteristics of people with chronic fatigue syndrome. J Musculoskel Pain 18(2):127-137. People with chronic fatigue syndrome often have significant pain issues, and these must be treated by pain management strategies. Research has been focused on the fatigue, although five of the eight other symptoms commonly reported are pain-related. [Patients reported pain symptoms, including muscle tightness, associated with myofascial TrPs and nerve entrapment. It would be of great importance to find out the percentage of chronic fatigue syndrome patients who also have co-existing myofascial TrPs. Myofascial pain may be an important and treatable interactive condition contributing not only to the pain but also to the fatigue. DJS]

Martenson ME, Halawa OI, Tonsfeldt KJ et al. 2015. A possible neural mechanism for photosensitivity in chronic pain. Pain. [Dec 9 Epub ahead of print.] "Patients with functional pain disorders often complain of generalized sensory hypersensitivity, finding sounds, smells, or even everyday light aversive. The neural basis for this aversion is unknown, but cannot be attributed to a general increase in cortical sensory processing. Here we quantified the threshold for aversion to light in patients with fibromyalgia, a pain disorder thought to reflect dysregulation of brain pain-modulating systems. These individuals expressed discomfort at light levels substantially lower than healthy controls. Complementary studies in lightly anesthetized rat demonstrated that a subset of identified pain-modulating neurons in the rostral ventromedial medulla unexpectedly responds to light. Approximately half of the pain-facilitating "ON-cells" and pain-inhibiting "OFF-cells" sampled exhibited a change in firing with light exposure, shifting the system to a pro-nociceptive state with activation of ON-cells and suppression of OFF-cell firing. The change in neuronal firing did not require a trigeminal or posterior thalamic relay, but was blocked by inactivation of the olivary pretectal nucleus. Light exposure also resulted in a measurable but modest decrease in the threshold for heat-evoked paw withdrawal, as would be expected with engagement of this pain-modulating circuitry. These data demonstrate integration of information about light intensity with somatic input at the level of single pain-modulating neurons in the brainstem of the rat under basal conditions. Taken together, our findings in rodents and humans provide a novel mechanism for abnormal photosensitivity, and suggest that light has the potential to engage pain-modulating systems such that normally innocuous inputs are perceived as aversive or even painful."

Martin DP, Sletten CD, Williams BA et al. 2006.  Improvement in fibromyalgia symptoms with acupuncture: results of a randomized controlled trial.  Mayo Clin Proc. 81(6):749-757.  “We found that acupuncture significantly improved symptoms of fibromyalgia.  Symptomatic improvement was not restricted to pain relief and was most significant for fatigue and anxiety.”  [The subset of FMs patients who have anxiety and fatigue may benefit from specific acupuncture therapy.  DJS]

Martín F, Blanco-Suárez M, Zambrano P, et al. Increased gut permeability and bacterial translocation are associated with fibromyalgia and myalgic encephalomyelitis/chronic fatigue syndrome: implications for disease-related biomarker discovery. Front Immunol. 2023 Sep 7:14:1253121. Biomarkers of intestinal barrier function and inflammation were associated with autonomic dysfunction assessed by COMPASS-31 scores in FM and ME/CFS respectively. Anti-β-LGB antibodies, ZO-1, LPS, and sCD14 may be putative predictors of intestinal barrier dysfunction in these cohorts.

Martin KL, Blizzard L, Srikanth VK et al. 2013. Cognitive Function Modifies the Effect of Physiological Function on the Risk of Multiple Falls--A Population-Based Study. J Gerontol A Biol Sci Med Sci. [Feb 14 Epub ahead of print]. "A range of cognitive (executive function/attention, memory, processing speed, and visuospatial ability) and physiological functions (vision, proprioception, sway, leg strength, reaction time) were measured using standardized tests in 386 randomly selected adults aged 60-86. Incident falls were recorded over 12 months….Preventing falls due to physiological impairments in community-dwelling older people may need to be tailored based on cognitive impairment, a key factor in their inability to compensate for physical decline."

Martin S, Chandran A, Zografos L et al. 2009.  Evaluation of the impact of fibromyalgia on patients’ sleep and the content validity of two sleep scales.  Health Qual Life Outcomes. 7(1):64.  “This study demonstrates the significant impact that FM has on patients’ lives, particularly sleep.”  [A sleep study is an important part of FM evaluation, and may uncover several treatable perpetuating factors that are impacting the patient’s quality of life. DJS]

Martin-Martínez JP, Villafaina S, Collado-Mateo D et al. 2020. Impact of cognitive tasks on biomechanical and kinematic parameters of gait in women with fibromyalgia: A cross-sectional study. Physiol Behav. Sep 18;227:113171." Adding a cognitive task to a primary motor task affects the walking motor pattern in women with FM, making it more stable and safer walking pattern when the attention is focused on two simultaneous tasks".

Martín-Pintado-Zugasti A, Mayoral Del Moral O, Gerwin RD et al. 2018. Post-needling soreness after myofascial trigger point dry needling: Current status and future research. J Bodyw Mov Ther. 22(4):941-946. "MTrP dry needling procedures have shown to be associated with post-needling soreness, which is thought to be a consequence of the neuromuscular damage, and hemorrhagic and inflammatory reaction generated by the needle. Postneedling soreness is a very frequent effect after deep dry needling, usually lasting less than 72?h. It may not be especially distressing for most patients. However, patients presenting with higher levels of post-needling soreness, not perceiving dry needling effectiveness in the first session, or not having high myofascial pain intensity before treatment, could be the most likely to find post-needling soreness more distressing, functionally limiting and to abandon treatment. Future research should assess the clinical relevance of post-needling soreness. Post-needling soreness should be considered when investigating dry needling effectiveness since it could overlie the original myofascial pain and influence the patients' pain ratings." [The presence of FM and other central sensitizatiostates could affect post-needling pain significantly. DJS]

Martín-Pintado-Zugasti A, Pecos-Martin D, Rodríguez-Fernandez AL et al. 2015. Ischemic compression after dry needling of a latent myofascial trigger point reduces postneedling soreness intensity and duration. PM R. 7(10):1026-1034. A selection of non-symptomatic university students (40 men and 50 women) aged 18 to 39 years were tested to see if compression after dry needling would help minimize post-injection soreness. One latent trigger point in the upper trapezius was given dry needling in this randomized, double-blind, placebo-controlled trial with 72-hour follow-up. Subjects were randomly divided into groups. One received compression after dry needling, one received sham compression (not on but near needle site), and one that did not receive compression (control group). Subjects were checked for postneedling soreness and cervical range of motion. Subjects in the compression group showed significantly lower postneedling soreness than the placebo and the control group subjects immediately after treatment, and those in the dry needling plus compression group had significantly lower postneedling soreness. All subjects significantly improved range of motion in the neck in contralateral lateroflexion and both homolateral and contralateral rotations, but only the improvements found in the IC group reached the minimal detectable change. Compression immediately after dry needling significantly reduced post injection soreness.

Martín-Pintado-Zugasti A, Rodríguez-Fernandez AL, Fernandez-Carnero J2. 2016. Postneedling soreness after deep dry needling of a latent myofascial trigger point in the upper trapezius muscle: Characteristics, sex differences and associated factors. J Back Musculoskelet Rehabil. 29(2):301-308. "Soreness and hyperalgesia are present in all subjects after dry needling of a latent MTrP in the upper trapezius muscle. Women exhibited higher intensity of postneedling soreness than men."

Martinez MP, Miro E, Sanchez AI et al. 2013. Cognitive-behavioral therapy for insomnia and sleep hygiene in fibromyalgia: a randomized controlled trial. J Behav Med. [Jun 7 Epub ahead of print]. "The CBT-I (cognitive-behavioral therapy for insomnia) group reported significant improvements at post-treatment in several sleep variables, fatigue, daily functioning, pain catastrophizing, anxiety and depression. The SH (sleep hygiene) group only improved significantly in subjective sleep quality. Patients in the CBT-I group showed significantly greater changes than those in the SH group in most outcome measures. The findings underscore the usefulness of CBT-I in the multidisciplinary management of FM."

Martinez-Jauand M, Sitges C, Femenia J et al. 2013. Age-of-onset of menopause is associated with enhanced painful and non-painful sensitivity in fibromyalgia. Clin Rheumatol. 32(7):975-981. "Fibromyalgia (FM) is a chronic pain condition characterized by high prevalence in women. In particular, estrogen deficit has been considered as a potentially promoting factor of FM symptoms. This study was aimed to examine the relationship between age-of-onset of menopause and pain sensitivity in FM. For this purpose, pain sensitivity was assessed in 74 FM and 32 pain-free control women. All participants were postmenopausal and underwent a detailed semi-structured clinical interview, including data about menopause transition, previous history of hysterectomy or ovariectomy, and menses time. Participants were divided into two groups depending on age-of-onset of menopause: early menopause [<49 years] vs. late menopause [>49 years]. Pain and non-pain thresholds were assessed by using cold, heat, mechanical, and electrical stimulation. FM women showed higher overall pain sensitivity as compared with healthy subjects. FM women with early age-of-onset of menopause displayed greater pain and non-pain sensitivity than women with late age-of-onset of menopause, whereas no differences were observed in healthy women due to age-of-onset of menopause. These results suggest that an early transition to menopause (shortening the time of exposure to estrogens) may influence pain hypersensitivity and could be related to aggravation of FM symptoms."

Martinez-Jauand M, Sitges C, Rodriguez V et al. 2012. Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene. Eur J Pain. [Apr 24 Epub ahead of print]. "Recent evidence suggests that genetic factors might contribute to individual differences in pain sensitivity, risk for developing clinical pain conditions and efficacy of pain treatments. The purpose of the present study was to investigate the relationship of three common haplotypes of COMT gene affecting the metabolism of catecholamines on pain sensitivity in patients with fibromyalgia (FM)….According with previous research, our findings revealed that haplotypes of the COMT gene and genotypes of the Val158Met polymorphism play a key role on pain sensitivity in FM patients."

Martínez-Jiménez EM, Losa-Iglesias ME, Mazoteras-Pardo V, et al. Dry needling of the flexor digitorum brevis muscle reduces postural control in standing: A pre-post stabilometric study. J Anat. 2023 Mar 16. Online ahead of print. "Dry needling therapy application in FDB (flexor digitorum brevis) muscle reduces standing postural control with eyes closed."

Martinez-Lavín M. 2018. Fibromyalgia and small fiber neuropathy: the plot thickens! Clin Rheumatol. [Sep 20 Epub ahead of print] "Predominant rheumatology thinking proposes fibromyalgia as a "centralized pain syndrome." An alternative hypothesis views fibromyalgia as a stress-related dysautonomia with neuropathic pain features. Dorsal root ganglia may be the key autonomic-nociceptive short-circuit sites. The recent recognition of small fiber neuropathy in a large subgroup of fibromyalgia patients reinforces the dysautonomia-neuropathic hypothesis and validates fibromyalgia pain. These new findings support fibromyalgia as a primarily neurological entity, nevertheless, rheumatologist will likely remain the best equipped specialist to diagnose fibromyalgia and differentiate it from other multi-symptomatic rheumatic syndromes. [Must fibromyalgia be central sensitization or dysautonomia? Why not both? There are also the autonomic concomitants of co-existing myofascial trigger points to consider. It would be interesting to have the areas of small fiber neuropathy in FM patients assessed for small fiber myofascial nerve entrapment. DJS]

Martinez-Lavin M. 2018. HPV vaccination syndrome: A clinical mirage, or a new tragic fibromyalgia model. Reumatol Clin. [Mar 13 Epub ahead of print] [Article in English, Spanish] "Independent investigators have described the onset of a chronic painful dysautonomic syndrome soon after human papillomavirus (HPV) vaccination. The veracity of this syndrome is hotly debated. Many of the reported post-HPV vaccination cases fulfill fibromyalgia diagnostic criteria. This article discusses the arguments favoring the existence of a syndrome associated to HPV vaccination. We propose that fibromyalgia dysautonomic-neuropathic model could help in the diagnostic and therapeutic process in those patients in whom the onset of a painful chronic illness began after HPV immunization. On the other hand, if its veracity is corroborated, HPV vaccination syndrome may become a new tragic fibromyalgia model." Free Article [This suggests that there may be a possibility of the HPV being an initiating factor of fibromyalgia, or at least a fibromyalgia-like illness. The author indicated in personal correspondence that the predisposition to develop the fibro-like illness seems to be a personal predisposition, but it is too early to tell if it is genetic.DJS]

Martinez-Lavin M. 2014. Fibromyalgia-like illness in 2 girls after human papillomavirus vaccination. J Clin Rheumatol 20(7):392-393.

Martinez-Lavin M. 2012. Fibromyalgia: When Distress Becomes (Un)sympathetic Pain. Pain Res Treat. 2012:981565. [Epub 2011 Sep 19] "...in fibromyalgia, distress could be converted into pain through forced hyperactivity of the sympathetic component of the stress response system."

Martinez-Lavin M. 2004.  Fibromyalgia as a sympathetically maintained pain syndrome.  Curr Pain Headache Rep. 8(5):385-389.  “...patients with FM display signs of relentless sympathetic hyperalgesia...”

Martinez-Lavin, M. 2002. The autonomic nervous system, and fibromyalgia. J Musculoskel Pain 10(1/2):221-228. Fibromyalgia is a multisystem illness. Many researchers have found indications that fibromyalgia is a form of autonomic nervous system dysfunction.

Martinez-Lavin, M. 2002. Management of dysautonomia in fibromyalgia. Rheum Dis Clin North Am 28(2):379-87. "The realization of dysautonomia in FM has opened the possibility for new and different therapeutic interventions.  Much more research is needed to better define the role of ANS in the pathogenesis of FM.  If this research supports current hypotheses, therapeutic trials with disciplines and substances intended to correct autonomic dysfunction will be indicated."

Martínez-Lavín M, Vargas A, Silveira LH et al. 2020. Complex Regional Pain Syndrome evolving to full-blown fibromyalgia: A proposal of common mechanisms. Clin Rheumatol. [Feb 5 Epub ahead of print] "Similar mechanisms have been recently put forward to explain the development of CRPS and fibromyalgia including dorsal root ganglia (DRG) hyperexcitability and small fiber neuropathy…. This was a review of medical records and PubMed search on the relationship between CRPS-fibromyalgia with DRG and small nerve fiber neuropathy…. Our 3 cases displayed over time orderly evolution from CRPS to fibromyalgia…. Clinicians should be aware that CRPS can evolve to full-blown fibromyalgia. Spreading of neuroinflammation through DRG glial cell activation could theoretically explain the transformation from regional to generalized complex pain syndrome." [Patients with FM and/or chronic myofascial pain and dysfunction may also be at risk for developing CRPS. Observation indicates that in some patients the spread of CRPS can be reversed, if caught early and the associated TrPs are treated. DJS]

Martinez-Martínez LA, Pérez LF, Becerril-Mendoza LT. 2017. Ambroxol for fibromyalgia: one group pretest-posttest open-label pilot study. Clin Rheumatol. [May 2 Epub ahead of print] "A consistent line of investigation proposes that fibromyalgia is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia sodium channels may play a major role in fibromyalgia pain transmission. Ambroxol is a secretolytic agent used in the treatment of various airway disorders. Recently, it was discovered that this compound is also an efficient sodium channel blocker with potent anti-neuropathic pain properties….Side effects were minor. In this pilot study, the use of ambroxol was associated to decreased fibromyalgia pain and improved fibromyalgia symptoms. The open nature of our study does not allow extracting the placebo effect from the positive results. The drug was well tolerated. Ambroxol newly recognized pharmacological properties could theoretically interfere with fibromyalgia pain pathways. Dose escalating-controlled studies seem warranted."

Martinez-Martos JM, Correa-Rodriguez M, Rus A et al. 2019. Altered serum oxytocinase and enkephalin-degrading aminopeptidase activities in patients with fibromyalgia. Biol Res Nurs. May 26:1099800419854207. [Epub ahead of print] "Our findings show that serum oxytocinase activity is increased in patients with FM, which could alter the metabolism of peptides with analgesic effects such as oxytocin and enkephalins. The determination of serum oxytocinase activity may aid in FM diagnosis. Additionally, we have identified a subpopulation of FM patients with abnormally low serum EDA (enkephalin-degrading aminopeptidase) activity."

Martinez-Moragon E, Plaza V, Torres I et al. 2017. Fibromyalgia as a cause of uncontrolled asthma: a case-controlled multicenter study. Curr Med Res Opin. 12:1-15."Fibromyalgia in patients with asthma influences the poor control of the respiratory disease and is associated with altered perception of dyspnea, hyperventilation syndrome, high prevalence of depression and anxiety, and impaired quality of life…. Fibromyalgia may be considered a risk factor for uncontrolled asthma in patients suffering from asthma and fibromyalgia concomitantly."

Martín-Hernandez D, Tendilla-Beltran H, Madrigal JLM, et al. 2018. Chronic mild stress alters kynurenine pathways changing the glutamate neurotransmission in frontal cortex of rats. Mol Neurobiol. May 3. [Epub ahead of print]" Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD)...Our research examines the link between CMS-induced pro-inflammatory cytokines and the kynurenine pathway; it shows that CMS (chronic mild stress) alters the kynurenine pathway in rat FC (frontal cortex). Importantly, it also reveals the ability of classic ADs (antidepressants) to prevent potentially harmful situations related to the brain scenario caused by CMS." [A subset of fibromyalgia patients utilize the kynurenine metabolic pathway to hijack 5-HTP, creating quinolinic acid (a nerve toxin) instead of serotonin). This research may be relevant. This study from Spain may shed light on how even mild stress can provoke a biochemical inflammatory stress response, at least in rats. DJS]

Martini A, Schweiger V, Del Balzo G et al. 2018. Epidemiological, pharmacological and sociodemographic characterisation of a population of 386 fibromyalgic patients referred to a tertiary pain centre in Italy. Clin Exp Rheumatol. [Aug 29 Epub ahead of print] "Fibromyalgia's prevalence in Italy is about 4%. Apart from widespread pain and the three main conditions related to fibromyalgia that are included in its diagnosis (fatigue, unrefreshing sleep and cognitive disorders disturbances), there are a number of minor symptoms that have been associated to fibromyalgia. The current study aimed to characterise fibromyalgic patients referring to a single tertiary pain centre not only for sociodemographic data, but also with special attention on pharmacological history and "minor" symptoms. "Minor" refers to the group of symptoms that were frequently associated and reported with fibromyalgia in various epidemiological studies but are not required for diagnosis. A retrospective analysis was made on 386 patients with confirmed diagnosis based on the 2010 modified criteria. Our results partially confirmed known sociodemographic data, but the prevalence of some "minor" symptoms are impressively high in our population." [This paper is the first to specify and quantify many coexisting symptoms clearly and comprehensively. Many of these symptoms may be indicative of myofascial trigger points. Many important observations are included, such as the frequency in FM patients of drug hypersensitivity, headache, IBS, and the high number of FM patients with breast cancer. The missing link again could be partially due to coexisting myofascial trigger points causing irritation of the CNS. DJS]

Martino, A. M. 1998. In search of a new ethic for treating patients with chronic pain: What can medical boards do? J Law, Medicine & Ethics 26(4):332-49.

Martín-Pintado-Zugasti A, Fernandez-Carnero J, Leon-Hernandez JV et al. 2018. Postneedling soreness and tenderness after different dosages of dry needling of an active myofascial trigger point in patients with neck pain: a randomised controlled trial. PM R. May 29. [Epub ahead of print] "Postneedling soreness is present in most of subjects after DDN (deep dry needling) of active MTrPs. The groups in which DDN was performed eliciting LTRs (local twitch responses) exhibited greater post-needling soreness. The number of needle insertions was associated with postneedling soreness but psychological factors did not seem to play a relevant role on its perception."

Martin-Pintado-Zugasti A, Pecos-Martin D, Rodriguez-Fernandez AL et al. 2015. Ischemic compression after dry needling of a latent myofascial trigger point reduces post-needling soreness intensity and duration. PM R. [Mar 30 Epub ahead of print.] "IC can potentially be added immediately after dry needling of MTrPs in the upper trapezius muscle because it has the effect of reducing postneedling soreness intensity and duration. The combination of dry needling and IC seems to improve CROM (cervical range of motion) in homolateral and contralateral cervical rotation movements." [The subjects in this study did not have chronic pain. DJS]

Martín-Pintado-Zugasti A, Rodríguez-Fernandez AL, Fernandez-Carnero J2. 2016. Postneedling soreness after deep dry needling of a latent myofascial trigger point in the upper trapezius muscle: Characteristics, sex differences and associated factors. J Back Musculoskelet Rehabil. 29(2):301-308. "Soreness and hyperalgesia are present in all subjects after dry needling of a latent MTrP in the upper trapezius muscle. Women exhibited higher intensity of postneedling soreness than men." [The subjects in this study were healthy and the trigger points were latent. DJS]

Martins IPM, Bodenmuller PHK, de Oliveira Mello DB, et al. 2021. COVID-19 pandemic and exercising: a cross-sectional study with 1156 patients with fibromyalgia. Rev Assoc Med Bras (1992). Oct; 67(10):1392-1396. "A high proportion of patients with fibromyalgia stopped exercising during COVID-19 pandemic; as a result, the impact of the disease during this period was worse among those not practicing exercises."

Martucci KT, Weber 2nd KA, Mackey SC, et al. 2021. Spinal cord resting state activity in individuals with fibromyalgia who take opioids. Front Neurol. Aug 4;12:694271. "While spinal cord mechanisms of chronic pain have been extensively characterized in animal models and in vitro, to date, research in patients with chronic pain has focused only very minimally on the spinal cord…. We hypothesized that the opioid (vs. non-opioid) patient group would show greater regional alterations in spinal cord activity (i.e., the amplitude of low frequency fluctuations or ALFF, a measure of regional spinal cord activity). However, we found that regional spinal cord activity in the opioid group was more similar to healthy controls, while regional spinal cord activity in the non-opioid group showed more pronounced differences (i.e., ventral increases and dorsal decreases in regional ALFF) vs. healthy controls. Across patient groups, self-reported fatigue correlated with regional differences in spinal cord activity. Additionally, spinal cord functional connectivity and graph metrics did not differ among groups. Our findings suggest that, contrary to our main hypothesis, patients with fibromyalgia who take opioids do not have greater alterations in regional spinal cord activity."

Martucci KT, Weber KA 2nd, Mackey SC. 2018. Altered cervical spinal cord resting state activity in fibromyalgia. Arthritis Rheumatol. [Oct 3 Epub ahead of print] "Our results indicate unbalanced activity between the ventral and dorsal cervical spinal cord in fibromyalgia. Increased ventral neural processes and decreased dorsal neural processes may reflect the presence of central sensitization and contribute to fatigue and other bodily symptoms in fibromyalgia."

Marvisi M, Balzarini L, Mancini C et al. 2015. Fibromyalgia is frequent in obstructive sleep apnea and responds to CPAP therapy. Eur J Intern Med. [Jun 28 Epub ahead of print.]

Marwick, C. 1999. New advocates of adequate treatment say have no fear of pain or of prosecution. JAMA 281:406-407.

Masand, P. S. and S. Gupta. 1999. Selective serotonin-reuptake inhibitors: an update. Harv Rev Psychiatry 7(2):69-84.

Mascia P, Brown BR, Friedman S. 2003.  Toothache of nonodontogenic origin: a case report.  J Endod. 29(9):608-610.  “This article describes the diagnosis and treatment of a patient exhibiting nonodontogenic tooth pain.  A 25-year-old female patient presented to postgraduate endodontics, SUNY at Stony Brook, for evaluation and treatment of pain associated with the upper and lower left quadrants.  After thorough intraoral and extraoral examinations, it was determined that the pain was referred to the dentition from a trigger point in the masseter muscle.  An extraoral injection of 3% Carbocaine was administered into the trigger point, and the pain abated within 5 minutes.  The patient has experienced no recurrence of this pain for 12 months.  Consideration of nonodontogenic dental pain should be included in a differential diagnosis.”

Mascia P, Brown BR, Friedman S. 2003.  Toothache of nonodontogenic origin: a case report.  J Endod 29(9):608-10. These authors found that a masseter trigger point was the source of tooth pain in this patient.  The patient had immediate relief after trigger point injection, with no recurrence of the pain. Dental practitioners need myofascial medicine as part of their training and their differential diagnosis.   

Mason JS, Tansey KA, Westrick RB. 2014. Treatment of subacute posterior knee pain in an adolescent ballet dancer utilizing trigger point dry needling: a case report. Int J Sports Phys Ther. 9(1):116-124. "The subject was a 16-year-old female competitive ballet dancer referred to physical therapy with a two month history of right posterior knee pain. Palpation identified MTPs which reproduced the patient's primary symptoms. In addition to an exercise program promoting lower extremity flexibility and hip stability, the subject was treated with DN to the right gastrocnemius, soleus, and popliteus muscles….The patient was able to return to high level dance training and competition without physical limitations and resumed pre-injury dynamic movement activities including dancing, running, jumping, and pivoting without pain. DN can be an effective and efficient intervention to assist patients in decreasing pain and returning to high intensity physical activity. Additional research is needed to determine if DN is effective for other body regions and has long-term positive outcomes."

Masralla, M., J. Haier and G. L. Nicolson. 1999. Multiple mycoplasmal infections detected in blood of patients with chronic fatigue syndrome and/or fibromyalgia syndrome. Eur J ClinMicrobiol Infect Dis 18(12):859-65.

Massey PB. 2007.  Reduction of fibromyalgia symptoms through intravenous nutrient therapy: results of a pilot clinical trial.  Altern Ther Health Med. 13(3):32-34.  “IVNT appears to be safe to reduce FM symptoms.”  The patients in this study had FM for at least 8 years and had no significant, lasting relief with conventional therapies.

Mastrangelo F, Frydas I, Ronconi G et al. 2018. Low-grade chronic inflammation mediated by mast cells in fibromyalgia: role of IL-37. J Biol Regul Homeost Agents. 32(2):195-198. "In FM there is an increase in reactivity of central neurons with increased sensitivity localized mainly in the CNS. Mast cells are involved in FM by releasing proinflammatory cytokines, chemokines, chemical mediators, and PGD2. TNF is a cytokine generated by MCs and its level is higher in FM. The inhibition of pro-inflammatory IL-1 family members and TNF by IL-37 in FM could have a therapeutic effect. Here, we report for the first time the relationship between MCs, inflammatory cytokines and the new anti-inflammatory cytokine IL-37 in FM."

Mataran-Penarrocha GA, Castro-Sanchez AM, Garcia GC et al. 2009.  Influence of craniosacral therapy on anxiety, depression and quality of life in patients with fibromyalgia.  Evid Based Complement Alternat Med. [Sep 3 Epub ahead of print].  “Approaching fibromyalgia by means of craniosacral therapy contributes to improving anxiety and quality of life levels in these patients.”  [Craniosacral therapy can be a good way to integrate other therapies and calm the sympathetic nervous system. DJS]

Matarín Jimenez TM, Fernandez-Sola C, Hernandez-Padilla JM et al. 2017. Perceptions about the sexuality of women with fibromyalgia syndrome: a phenomenological study. J Adv Nurs. [Jan 25 Epub ahead of print.] "Three themes define the perception of sexuality for these women: (1) Physical impact: don't touch, don't look; (2) Sexuality and identity: fighting against their loss; (3) Impact on the relationship: sexuality as a way of connecting the couple…. Despite limitations, sexuality is important for the identity and quality of life of women with fibromyalgia syndrome. Together with the physical symptomology, guilt, fear and a lack of understanding compromise the coping process. Women need the support of their partner, their socio-family environment and health professionals. Nurses can aid the successful adjustment to sexual problems related to fibromyalgia syndrome."

Mathew PG, Cutrer FM, Garza I. 2016. A touchy subject: an assessment of cutaneous allodynia in a chronic migraine population. J Pain Res. 9:101-104. "Cutaneous allodynia (CA) is a common feature of migraine, which has a complex underlying pathophysiology that is not well understood. In addition to pain, photophobia, phonophobia, osmophobia, nausea, and vomiting, CA can contribute to the overall disability caused by migraine…." According to this Mayo Clinic study: "CA appears to be quite prevalent, at ˜90%, among female patients with chronic migraine." Free PMC Article

Mathias K, Amarnani A, Pal N, et al. Chronic pain in patients with rheumatoid arthritis. Curr Pain Headache Rep. 2021 Jul 16;25(9):59. "Chronic pain associated with RA typically occurs in patients with anxiety, female sex, and elevated inflammatory status. Up to 50% of these patients are thought to have chronic pain despite appropriate inflammatory suppression, typically due to peripheral and central sensitization as well as secondary OA and FM. In addition to the standard-of-care management for OA and FM, patients with RA and chronic pain benefit from behavioral and psychological treatment options. Moreover, early and multimodal therapies, including non-pharmacological, pharmacological, interventional, and surgical strategies, exist, albeit with varying efficacy, to help suppress inflammation, provide necessary analgesia, and optimize functional outcomes."

Mathieson L, Hirani SP, Epstein R et al. 2009.  Laryngeal manual therapy: a preliminary study to examine its treatment effects in the management of muscle tension dysphonia.  J Voice. 23(3):353-366.  Manual therapy can often relieve what is called “muscle tension dysphonia.”  [This indicates that a significant portion of the problem may be due to the presence of TrPs in the laryngeal and related muscles.  People working in this field must be made aware of this situation.  It would be a win/win scenario for all concerned.  DJS]

Mathieu N. 2009. [Somatic comorbidities in irritable bowel syndrome: fibromyalgia, chronic fatigue syndrome, and interstitial cystitis]  Gastroenterol Clin Biol. 33 Suppl 1:S17-25. [French]  “Fibromyalgia, chronic fatigue syndrome, and interstitial cystitis frequently overlap with irritable bowel syndrome (IBS).  There is a positive correlation between the incidence of these comorbidities and increased health care seeking, reduction in quality of life, and higher levels of mood disorders, which raises the question of a common underlying pathophysiology.  A possible central hypersensitization disorder seems to be particularly involved in the dysfunction of bidirectional neural pathways and viscerovisceral cross-interactions within the CNS, thus explaining these many extraintestinal manifestations in IBS.”

Matilainen V, Laakso M, Hirsso P. 2013. Hair loss, insulin resistance, and heredity in middle-age women. A population-based study. J Cardiovasc Risk. 10(3):227-231. Insulin resistance is associated with "…large waist and neck circumferences, abdominal obesity by waist to hip ration, mean insulin concentration or urinary albumin to creatinine ratio. Although extensive hair loss has been linked to men with insulin resistance, this study found it is present in women too. Female hair loss has been linked to hyper-androgenism, hirsutism, and polycystic ovary syndrome. These researchers found a 31.2% presence of extensive hair loss in patients with insulin resistance. Women in the highest percentiles of waist and neck circumference had greater risk of hair loss".

Matsel K, Davies C, Uhl T. 2020. The long-term effectiveness of trigger point dry needling and exercise for individuals with shoulder pain: A critically appraised topic. J Sport Rehabil. Sep 1;1-6. "Improvement in long-term pain and function can be expected regardless of the addition of TDN to an evidence-based exercise program for patients with shoulder pain. Clinical Bottom Line: Either TDN or an evidence-based therapeutic exercise program elicits improved long-term pain and disability reduction in patients with shoulder pain, which suggests that clinicians can confidently use either approach with their patients."

Matsuda JB, Barbosa FR, Morel LJ et al. 2010. [Serotonin receptor (5-HT 2A) and catechol-O-methyltransferase (COMT) gene polymorphisms: Triggers of fibromyalgia?] Rev Bras Reumatol. 50(2):141-145. [Portuguese] "The L/L genotype was more frequent among fibromyalgia patients. Though considering a polygenic situation and environmental factors, the molecular study of the rs4680 SNP of the COMT gene may be helpful to the identification of susceptible individuals."

Matsuda M, Imaoka T, Vomachka AJ et al. 2004.  Serotonin regulates mammary gland development via an autocrine-paracrine loop.  Dev Cell 6(2):193-203.  Dysfunctional serotonin signaling may be part of the reason some women with FMS experience problems nursing.  Nursing may begin normally, but the milk [production] hesitates or stops.

Matsumoto T, Chin K. 2019. Prevalence of sleep disturbances: Sleep disordered breathing, short sleep duration, and non-restorative sleep. Respir Investig. [Feb 28 Epub ahead of print] "Recently, interest in sleep disturbances, such as sleep disordered breathing (SDB), short sleep duration, and non-restorative sleep (NRS), has been increasing. The potentially large public health implications of sleep disturbances indicate a need to determine their prevalence in a general population. This review describes the characteristics of population-based sleep cohorts from past to present. Unavoidable methodological and baseline characteristic heterogeneity was found between studies. The prevalence of SDB (apnea hypopnea index (AHI), respiratory disturbance index (RDI), or oxygen desaturation index (ODI) ≥5/h) was 24.0-83.8% in men and 9.0-76.6% in women, and that of moderate-to-severe SDB (AHI, RDI, or ODI ≥15/h) was 7.2-67.2% in men and 4.0-50.9% in women.… An association between SDB, short sleep duration, and NRS has recently been suggested. To gain a better understanding of the burden of sleep disturbances, a consensus on the definition of several sleep disturbances is needed, as methodological heterogeneity exists, including SDB scoring rules, subjective versus objective data collection for short sleep duration, and the definition of NRS itself." [Lack of restorative sleep is common in FM. It is not unusual for FM patients to have multiple sleep dysfunctions. From my experience, neither is it unusual for patients who have chronic pain and fatigue to remain without good clinical polysomnography, nor for those who have had polysomnography to have care providers who have ignored sleep architecture and focus only on sleep apneas. Defining common sleep dysfunctions is an important step in changing this state. DJS]

Matsutani LA, Marques AP, Ferreira EA et al. 2007.  Effectiveness of muscle stretching exercises with and without laser therapy at tender points for patients with fibromyalgia.  Clin Exp Rheumatol. 25(3):410-415.  “Laser therapy has not shown advantages when added to muscle stretching exercises.”

Matthews CA, Deveshwar SP, Evans RJ et al. 2019. Small fiber polyneuropathy as a potential therapeutic target in interstitial cystitis/bladder pain syndrome. Int Urogynecol J. [Jun 25 Epub ahead of print] Interstitial cystitis/bladder pain syndrome (IC/BPS) and fibromyalgia (FM) are frequently co-occurring medical diagnoses in patients referred to the urology clinic for secondary and tertiary treatment options….This finding of SFPN provides a therapeutic target for FM and in this article we hypothesize and provide rationale for the idea that this same phenomenon (SFPN) might explain, in some IC/BPS patients, the finding of widespread pain and likewise provide a therapeutic target for these patients.

Mattozzi I. 2015. [Conservative treatment of cervical radiculopathy with 5% lidocaine medicated plaster.] Minerva Med. 105(1):1-7.[Article in Italian] Cervical radiculopathy is a mixed pain syndrome characterized by neuropathic, skeletal and myofascial pain….A retrospective study was carried out on 60 patients, of which 30 were treated with mesotherapy and 30 were treated with 5% lidocaine medicated plaster. Data for a total of 30 days observation were collected from the patient medical records. In particular, besides medical history, intensity of pain, intensity of allodynia and pain were considered….For all analyzed parameters, both treatments were effective, but patients treated with 5% lidocaine medicated plaster showed faster control of the painful symptoms, an essential condition for an earlier rehabilitative treatment.

Mau, W. and H. Zeidler. 1999. [No title available]. Versicherungsmedizin 51(2):59-65 [German].

Maurer AJ, Lissounov A, Knezevic I et al. 2016. Pain and sex hormones: a review of current understanding. Pain Manag. [Mar 17 Epub ahead of print.] "Multiple epidemiologic studies have demonstrated an increased prevalence for women in several chronic pain disorders. Clinical and experimental investigations have consistently demonstrated sex-specific differences in pain sensitivity and pain threshold. Even though the underlying mechanisms responsible for these differences have not yet been elucidated, the logical possibility of gonadal hormone influence on nociceptive processing has garnered recent attention. In this review, we evaluated the complex literature regarding gonadal hormones and their influence on pain perception (and) the numerous functions of gonadal hormones, discussed the influence of these hormones on several common chronic pain syndromes (migraine, tension and cluster headaches, fibromyalgia, temporomandibular syndrome, rheumatoid arthritis and back pain, among others), and have attempted to draw conclusions from the available data."

Mawson AR, Croft AM. 2019. Gulf War Illness: Unifying Hypothesis for a Continuing Health Problem. Int J Environ Res Public Health. Jan 3;16(1). "An estimated 25%-32% of veterans of the 1991 Gulf War continue to experience multiple unexplained health problems known as Gulf War Illness (GWI). GWI encompasses chronic pain, musculoskeletal weakness, headache, fatigue, cognitive deficits, alterations in mood, and numerous multi-system complaints…. The features of GWI also overlap with those of fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity, in all of which liver dysfunction has been documented, suggesting a unifying hypothesis. It is proposed that multiple vaccinations, with concurrent or subsequent exposure to PB or additional chemical insults of a liver-damaging nature, plausibly explain the pathogenesis and the observed chronicity of GWI. The suggested mechanism for GWI is thus a chemically-induced impaired liver function, with the spillage of stored vitamin A compounds ("retinoids") into the circulation in toxic concentrations, resulting in an endogenous chronic form of hypervitaminosis A. Implications of the hypothesis are briefly reviewed." [Myofascial trigger points may be a missed co-existing condition, and treating them successfully may be able to provide some symptom relief. Adequate care must be taken not to release more substances from the myofascial than can be dealt with by the detoxification mechanisms of the body. DJS]

May A. 2009. [Chronic pain alters the structure of the brain.] Schmerz. [Oct 17 Epub ahead of print] [German]  “Local morphologic alterations of the brain in areas ascribable to the transmission of pain were recently detected in patients suffering from phantom pain, chronic back pain, irritable bowel syndrome, fibromyalgia and frequent headaches.  These alterations were different for each pain syndrome, but overlapped in the cingulated cortex, the orbit frontal cortex, the insula and dorsal pons. As it seems that chronic pain patients have a common ‘brain signature’ in areas known to be involved in pain regulation, the question arises whether these changes are the cause or the consequence of chronic pain.  The in vivo demonstration of a loss of brain gray matter in patients suffering from chronic pain compared to age and sex-matched healthy controls could represent the heavily discussed neuroanatomical substrate for pain memory.”

May. K. P. , S. G. West, M. R. Baker and D. W. Everett. 1993. Sleep apnea in male patients with the fibromyalgia syndrome. Am J Med 94(5):505-508.

Mayer, E. A., R. Fass and S. Fullerton. 1998. Intestinal and extraintestinal symptoms in

Mayer-Davis, E. J. , R. D’Agostino Jr., A. J. Karter, S. M. Haffner, M. J. Rewers, M. Saad and R. N. Bergman.1998. Intensity and amount of physical activity on relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study. JAMA 279(9):669-74.

Mayoral O, Salvat I, Martín MT et al. 2013. Efficacy of myofascial trigger point dry needling in the prevention of pain after total knee arthroplasty: a randomized, double-blinded, placebo-controlled trial. Evid Based Complement Alternat Med. 2013:694941. A single treatment of dry needling myofascial trigger points after anesthesia, before surgery for total knee arthroplasty, helped prevent residual pain. The pain was less for patients who had dry needling in the first month after surgery, and remained so at 6 month follow-up.

Mayoral del Moral O. 2010. Dry needling treatments for myofascial trigger points. J Musculoskel Pain. 18(4):411-416. "There exist different dry needling techniques that can be used in the treatment of trigger points. These techniques seem to be effective in treating this condition. There seems to be an increasing number of indications of these techniques within the context of myofascial pain syndrome. Dry needling techniques are rapidly expanding among healthcare providers. More research is needed to know the mechanisms of dry needling in order to improve its efficiency and the patients' tolerance of the techniques." There are multiple dry needling techniques, and all require training and experience.

Mayoral Del Moral O, Torres Lacomba M, Russell IJ et al. 2017. Validity and reliability of clinical examination in the diagnosis of myofascial pain syndrome and myofascial trigger points in upper quarter muscles. Pain Med. [Dec 15 Epub ahead of print] "Sensitivity and specificity showed high values for most examination tests in all muscles, which confirms the validity of clinical diagnostic criteria in the diagnosis of MPS.... Interrater reliability between two expert examiners identifying subjects with MPS involving upper quarter muscles exhibited substantial agreement. These results suggest that clinical criteria can be valid and reliable in the diagnosis of this condition."

McAllister SJ, Vincent A, Hassett AL et al. 2013. Psychological Resilience, Affective Mechanisms and Symptom Burden in a Tertiary-care Sample of Patients with Fibromyalgia. Stress Health. [Dec 26 Epub ahead of print.] "Our results suggest that improving affect through resiliency training could be studied as a modality for improving fibromyalgia symptom burden."

McAuley JH, Stanton TR, Kamper SJ et al. 2011. Psychological approaches have not been demonstrated to be effective for fibromyalgia. Pain. [Feb 10 Epub ahead of print].

McBeth J, Chiu YH, Silman AJ et al. 2005.  Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents.  Arthritis Res Ther. 7(5):R992-R1000.  “This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group.”  “We conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress.”

McBeth J, Lacey RJ, Wilkie R. 2014. Predictors of new-onset widespread pain in older adults: Results from a population-based prospective cohort study in the UK. Arthritis Rheumatol. 66(3):757-767. "Participants free of WP (as defined by the American College of Rheumatology 1990 criteria for fibromyalgia) were followed up for 3 years, and those with new-onset WP at follow-up were identified. …Of the factors measured in this study, nonrestorative sleep was the strongest independent predictor of new-onset WP."

McBeth, J., G. J. Macfarlane, S. Benjamin, S. Morris and A. J. Silman. 1999. The association between tender points, psychological distress, and adverse childhood experiences: a community-based study. Arthritis Rheum 42(7):1397-404.

McCabe CS, Cohen H, Hall J et al. 2009.  Somatosensory conflicts in complex regional pain syndrome type 1 and fibromyalgia syndrome.  Curr Rheumatol Rep. 11(6):461-465.  “The somatosensory system is an integral component of the motor control system that facilitates the recognition of location and experience of peripheral stimuli, as well as body part position and differentiation.  In chronic pain, this system may be disrupted by alterations in peripheral and cortical processing.  Clinical symptoms that accompany such changes can be difficult for patients to describe and health care practitioners to comprehend.  Patients with chronic pain conditions such as complex regional pain syndrome or fibromyalgia typically describe a diverse range of somatosensory changes.  This article describes how sensory information processing can become disturbed in fibromyalgia syndrome and complex regional pain syndrome and how symptoms can potentially be explained by the mechanisms that generate them.”  [This is a good study, and it is to be hoped that future studies will include myofascial TrPs. DJS]

McCabe CS, Cohen H, Blake DR. 2007. Somaesthetic disturbances in fibromyalgia are exaggerated by sensory motor conflict: implications for chronicity of the disease?  Rheumatology [Sep 1 Epub ahead of print]  “New perceptions included disorientation, pain, perceived changes in temperature, limb weight or body image.  Conclusions: Our findings support the hypothesis that motor-sensory conflict can exacerbate pain and sensory perceptions in those with FMS to a greater extent than in Hvs. [healthy volunteers]”

McCarberg B, Peppin J. 2019. Pain Pathways and Nervous System Plasticity: Learning and Memory in Pain. Pain Med. [Mar 13 Epub ahead of print] "Pain pathways represent a complex sensory system with cognitive, emotional, and behavioral influences. Anatomically, the hippocampus, amygdala, and anterior cortex-central to the encoding and consolidation of memory-are also implicated in experiential aspects of pain. Common neurotransmitters and similar mechanisms of neural plasticity (e.g., central sensitization, long-term potentiation) suggest a mechanistic overlap between chronic pain and memory. These anatomic and mechanistic correlates indicate that chronic pain and memory intimately interact on several levels. Longitudinal imaging studies suggest that spatiotemporal reorganization of brain activity accompanies the transition to chronic pain, during which the representation of pain gradually shifts from sensory to emotional and limbic structures.... The chronification of pain can be conceptualized as activity-induced plasticity of the limbic-cortical circuitry resulting in reorganization of the neocortex. The state of the limbic-cortical network determines whether nociceptive signals are transient or chronic by extinguishing pathways or amplifying signals that intensify the emotional component of nociceptive inputs. Thus, chronic pain can be seen as the persistence of the memory of pain and/or the inability to extinguish painful memories. Ideally, pharmacologic, physical, and/or psychological approaches should reverse the reorganization accompanying chronic pain."

McClaflin, R. R. 1994. Myofascial pain syndrome. Primary care strategies for early intervention. Postgrad Med 96(2):56-59.

McCrae CS, Mundt JM, Curtis AF et al. 2018. Gray matter changes following cognitive behavioral therapy for patients with comorbid fibromyalgia and insomnia: A pilot study. J Clin Sleep Med. 14(9):1595-1603. "Insomnia frequently co-occurs with fibromyalgia, which is associated with gray matter atrophy. We examined the effect of cognitive behavioral therapy for insomnia (CBT-I) and pain (CBT-P) on cortical thickness.... Our pilot study presents novel evidence suggesting that CBT-I may slow or reverse cortical gray matter atrophy in patients with fibromyalgia and insomnia." Free Article

McCrae CS, Williams J, Roditi D et al. 2018. Cognitive behavioral treatments for insomnia (CBT-I) and pain (CBT-P) in adults with comorbid chronic insomnia and fibromyalgia: Clinical outcomes from the SPIN randomized controlled trial. Sleep. [Nov 28 Epub ahead of print] "CBT-I (cognitive behavioral treatments for insomnia) and CBT-P (cognitive behavioral treatments for pain) improved self-reported insomnia symptoms. CBT-I prompted improvements of larger magnitude that were maintained. Neither treatment improved pain or mood. However, both prompted clinically meaningful, immediate pain reductions in one third of patients. Improvements persisted for CBT-I, suggesting CBT-I may provide better long-term pain reduction than CBT-P. Research identifying which patients benefit and mechanisms driving intervention effects is needed."

McCoy JG, Tartar JL Bebis AC et al. 2007.  Experimental sleep fragmentation impairs attentional set-shifting in rats.  Sleep 30(1):52-60.  “24 hour SI (sleep interruption) produced impairment in an attentional set shifting that is comparable to the executive function and cognitive deficits observed in humans with sleep apnea or after a night of experimental sleep fragmentation.”

McCracken, L. M. 1998. Learning to live with the pain: acceptance of pain predicts adjustment in persons with chronic pain. Pain 74(1):21-27.

McCrae CS, O'Shea AM, Boissoneault J et al. 2015. Fibromyalgia patients have reduced hippocampal volume compared with healthy controls. J Pain Res. 8:47-52. "Fibromyalgia patients frequently report cognitive abnormalities. As the hippocampus plays an important role in learning and memory, we determined whether individuals with fibromyalgia had smaller hippocampal volume compared with healthy control participants….Potential mechanisms for reduced hippocampal volume in fibromyalgia include abnormal glutamate excitatory neurotransmission and glucocorticoid dysfunction; these factors can lead to neuronal atrophy, through excitotoxicity, and disrupt neurogenesis in the hippocampus. Hippocampal atrophy may play a role in memory and cognitive complaints among fibromyalgia patients." Free PMC Article

McCray RE, Patton NJ. 1984.  Pain relief at trigger points: a comparison of moist heat and shortwave diathermy.  J Orthop Sports Phys Ther. 5(4):175-178.  “Both treatments were effective in relieving the pain of sensitive trigger points but shortwave diathermy was more effective at decreasing the sensitivity of both sensitive and moderate trigger points (P>0.0581).  The pressure algometer was shown to be a useful device for objectively measuring pain and may be useful in selecting the most effective type of treatment for trigger points.”

McDaniel WW. 2003.  Electroconvulsive therapy in complex regional pain syndromes.  J ETC 19(4):226-229.  “In one of the cases, concomitant fibromyalgia was not relieved during 2 separate series of ETC.”

McDowell JM, Kohut SH, Betts D. 2018. Safe acupuncture and dry needling during pregnancy: New Zealand physiotherapists' opinion and practice. J Integr Med. [Epub ahead of print] "NZ registered physiotherapists practicing acupuncture and/or DN were invited to participate in an electronic survey to examine their practice and level of understanding in regard to safe needling during pregnancy….Of 124 respondents, only 60 (48%) would needle pregnant women, with a further 66% of those still expressing safety concerns. NZ physiotherapists practicing DN only, were more likely to needle areas related to "forbidden" points in all trimesters. However, overall, NZ physiotherapists were less likely to needle "forbidden" points than their UK peers… Conflicting literature and a "fear of blame" influences NZ physiotherapists' decisions to offer needling (both acupuncture and DN) during pregnancy. Further training in this field is recommended to ensure safe practice and adequate provision of acupuncture treatment options for pregnant women suffering musculoskeletal pain, such as LBP and PGP."

McFadden, S. A. 1996. Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. Toxicology 111(1-3):43-65.

McGovney KD, Curtis AF, McCrae CS. Actigraphic physical activity, pain intensity, and polysomnographic sleep in fibromyalgia. Behav Sleep Med. 2023 Jul-Aug;21(4):383-396. "Greater morning and afternoon activity is associated with greater PSG sleep fragmentation and greater percentage stage 1 sleep in individuals with fibromyalgia and insomnia complaints, and the relationship between higher physical activity and greater percentage stage 1 is stronger for individuals with higher pain."

McGovney KD, Curtis AF, McCrae CS. Actigraphic physical activity, pain intensity, and polysomnographic sleep in fibromyalgia. Behav Sleep Med. 2022 Jul 20;1-14. "Fibromyalgia involves chronic pain and disrupted physical activity and sleep… This study examined whether objectively measured physical activity levels (via actigraphy), pain intensity, or their interaction are associated with polysomnographic sleep outcomes…. Greater morning and afternoon activity is associated with greater PSG sleep fragmentation and greater (percentage) stage 1 sleep in individuals with fibromyalgia and insomnia complaints, and the relationship between higher physical activity and greater (percentage) stage 1 is stronger for individuals with higher pain. Further studies examining causal pathways between physical activity, activity pacing, and sleep are warranted in fibromyalgia".

McGreevy K, Bottros MM, Raja SN. 2011. Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy. Eur J Pain Suppl. 5(2):365-372. This paper from Johns Hopkins states: "Chronic pain is the leading cause of disability in the United States. The transition from acute to persistent pain is thought to arise from maladaptive neuroplastic mechanisms involving three intertwined processes, peripheral sensitization, central sensitization, and descending modulation. Strategies aimed at preventing persistent pain may target such processes. Models for studying preventive strategies include persistent post-surgical pain (PPP), persistent post-trauma pain (PTP) and post-herpetic neuralgia (PHN). Such entities allow a more defined acute onset of tissue injury after which study of the long-term effects is more easily examined. In this review, we examine the pathophysiology, epidemiology, risk factors, and treatment strategies for the prevention of chronic pain using these models. Both pharmacological and interventional approaches are described, as well as a discussion of preventive strategies on the horizon."

McInnis OA, Matheson K, Anisman H. 2014. Living with the unexplained: Coping, distress, and depression among women with chronic fatigue syndrome (CFS) and/or fibromyalgia compared to an autoimmune disorder. Anxiety Stress Coping. [Jan 30 Epub ahead of print.] "Chronic fatigue syndrome (CFS) and fibromyalgia are disabling conditions without objective diagnostic tests, clear-cut treatments, or established etiologies. Those with the disorders are viewed suspiciously, and claims of malingering are common, thus promoting further distress…. High problem-focused coping was associated with low levels of depression and perceived distress in those with an autoimmune condition. In contrast, although CFS/fibromyalgia was also accompanied by higher depression scores and higher perceived distress, this occurred irrespective of problem-focused coping. It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia."

McInnis OA, McQuaid RJ, Bombay A et al. 2014. Finding benefit in stressful uncertain circumstances: relations to social support and stigma among women with unexplained illnesses. Stress. Dec 29:1-32. [Epub ahead of print.] "Living with a chronic illness can be challenging, but the ability to derive benefits and grow from this experience may enhance well-being. However, the possibility of obtaining such benefits may be dependent on the levels of stigmatization and lack of social support experienced by an individual as a result of the illness. Chronic fatigue syndrome (CFS) and fibromyalgia are chronic conditions that remain largely unexplained and those with these conditions must often contend with stigma and skepticism from others. Individuals with CFS/fibromyalgia often display stress-related biological alterations and the experience of stressful life events have been associated with illness development. The present study demonstrated that women with CFS/fibromyalgia (n=40) as well as community participants who were depressed/anxious (n=37), reported higher stigma levels than healthy women (n=33). Moreover, women with CFS/fibromyalgia and those with depression/anxiety also reported greater levels of stigma than women with a chronic yet more widely accepted condition (n=35; rheumatoid arthritis, osteoarthritis, and multiple sclerosis). Secrecy related to stigma among those with CFS/fibromyalgia declined with increased social support, but this was not apparent among those with other chronic conditions. In addition, posttraumatic growth was lower among women with CFS/fibromyalgia compared to those with other chronic conditions. Qualitative analysis examining both negative impacts and positive changes stemming from illness experience revealed many similarities between women with CFS/fibromyalgia and those with other chronic conditions, including elevated appreciation for life, personal growth, and compassion for others. However, women with CFS/fibromyalgia tended to report less positive change regarding interpersonal relationships compared to women with other chronic conditions. In general, unexplained illnesses were also accompanied by stigmatization which might ultimately contribute to women's lower ability to derive positive growth from their illness experience."

McKeever TM, Lewis SA, Smit HA et al. 2005.  The association of acetaminophen, aspirin, and ibuprofen with respiratory disease and lung function.  Am J Respir Crit Care Med. 171(9):966-971.  “Use of acetaminophen [but not aspirin or ibuprofen] is associated with an increased risk of asthma and COPD [chronic obstructive pulmonary disease], and with decreased lung function.”

McKernan LC, Finn MTM, Carr ER. 2017. Personality and affect when the central nervous system is sensitized: An analysis of Central Sensitization Syndromes in a substance use disorder population. Psychodyn Psychiatry. 45(3):385-409. "Functional somatic syndromes, or more recently termed central sensitivity syndromes (CSS), comprise a significant portion of the chronic pain population. Although it is evident that personality is intricately related to the pain experience, it has not been widely studied. This article examines the impact of CSS on the clinical presentation of individuals presenting to treatment for a substance use disorder (SUD), with an emphasis on personality and emotional functioning. We examined personality profiles of individuals presenting to treatment with SUD between three groups: those with a CSS…, non-CSS chronic pain…, and no pain …. Based on previous research and a psychodynamic conceptualization of CSS, we hypothesized that predictors of the presence of a CSS in this sample would be higher rates of overall anxiety, traumatic stress, perfectionistic traits, and a need for interpersonal closeness. Logistic regression analyses did not support our hypothesis. Exploratory analyses indicated which personality traits most strongly predicted the presence of CSS."

McKernan LC, Finn MTM, Crofford LJ, et al. Delivery of a group hypnosis protocol for managing chronic pain in outpatient integrative medicine. Int J Clin Exp Hypn. 2022 Jul 14;1-24. "This project evaluated changes in multiple outcome measures in persons with chronic pain treated with 8 weeks of group hypnosis…. The findings provide compelling preliminary evidence that a group format is an effective delivery system for teaching individual skills in using hypnosis for chronic pain management."

McKernan LC, Johnson BN, Crofford LJ et al. 2019. Posttraumatic stress symptoms mediate the effects of trauma exposure on clinical indicators of central sensitization in patients with chronic pain. Clin J Pain. [Feb 5 Epub ahead of print] "Evidence supports high rates of co-occurrence of posttraumatic stress disorder (PTSD) and chronic pain disorders involving central sensitization (CS)…. Both trauma exposure and PTSD symptoms were significantly associated with all three clinical indicators of CS. PTSD symptoms partially explained the relationship between trauma exposure and widespread pain, pain intensity, and polysomatic symptoms.

McKernan LC, Johnson BN, Reynolds WS et al. 2018. Posttraumatic stress disorder in interstitial cystitis/bladder pain syndrome: Relationship to patient phenotype and clinical practice implications. Neurourol Urodyn. [Oct 23 Epub ahead of print] "Although elevated, IC/BPS trauma exposure rates were equivalent to that of other chronic pain conditions in the sample. Despite this equivalence, in comparison, IC/BPS patients had significantly higher rates of PTSD symptoms, with 42% meeting provisional diagnostic criteria for PTSD. Among IC/BPS, those meeting provisional criteria for PTSD had significantly higher incidence of lifetime sexual abuse, childhood trauma, and presentations consistent with the widespread pain phenotype. In IC/BPS, there was no association between PTSD and genitourinary symptoms, but provisional PTSD was associated with more pain, emotional distress, and poorer quality of life." [Patients in this psychiatric mode study were not assessed for co-existing TrPs. DJS]

McKernan LC, Lenert MC, Crofford LJ et al. 2018. Outpatient engagement lowers predicted risk of suicide attempts in fibromyalgia. Arthritis Care Res (Hoboken). [Sep 7 Epub ahead of print] "Fibromyalgia (FM) patients are 10x more likely to die by suicide than the general population. The purpose of this study was to externally validate published models predicting suicidal ideation and attempts in FM and identify interpretable risk and protective factors for suicidality unique to FM... Risk factors specific to suicidal ideation included polysomatic complaints such as fatigue... dizziness... and weakness.... Risk factors specific to suicide attempt included obesity...and drug dependence... Per utilization analyses, those with FM and no suicidal ideation spent 3.5x more time in follow-up annually, and those without documented suicide attempts spent over 40x more time face-to-face with providers annually."

McKnite AM, Perez-Munoz ME, Lu L et al. 2012. Murine gut microbiota is defined by host genetics and modulates variation of metabolic traits. PLoS One. 7(6):e39191. "The gastrointestinal tract harbors a complex and diverse microbiota that has an important role in host metabolism. Microbial diversity is influenced by a combination of environmental and host genetic factors and is associated with several polygenic diseases. …Relationships between gut microflora, morphological and metabolic traits were uncovered, some potentially a result of common genetic sources of variation. Gut microorganisms may largely be determined by genetics."

McLean SA, Williams DA, Harris RE et al. 2005.  Momentary relationship between cortisol secretion and symptoms in patients with fibromyalgia.  Arthritis Rheum. 52(11):3660-3669.  “Among women with FM, pain symptoms early in the day are associated with variations in function of the hypothalamic-pituitary-adrenal axis.”

McLean SA, Clauw DJ. 2005.  Biomedical models of fibromyalgia.  Disabil Rehabil. 27(12):659-665.  “The tender point criteria for FM have resulted in the common misconception among health care professionals that this spectrum of disorders is limited to women with high degrees of psychological distress.  A hallmark of FM is the presence of non-nociceptive, central pain.  There is evidence of centrally augmented pain processing, which can be detected both with sensory testing and by more objective measures (e.g., evoked potentials, functional neuroimaging).  An appreciation of the neurobiological basis for these disorders, and an understanding of some of the abnormalities of pain processing present in patients with FM, will hopefully provide greater understanding of these patients.  It may also serve to decrease the level of frustration and improve the care experience of both chronic pain patients and physicians.”

McLean SA, Williams DA, Clauw DJ. 2005.  Fibromyalgia after motor vehicle collision: evidence and implications.  Traffic Inj Prev. 6(2):97-104.  “The evidence that MVC trauma may trigger FM meets established criteria for determining causality, and has a number of important implications, both for patient care, and for research into the pathophysiology and treatment of these disorders.”

McLennan MT. 2014. Interstitial Cystitis: Epidemiology, Pathophysiology, and Clinical Presentation. Obstet Gynecol Clin North Am. 41(3):385-395. "Interstitial cystitis, or painful bladder syndrome, can present with lower abdominal pain/discomfort and dyspareunia, and pain in any distribution of lower spinal nerves. Patients with this condition experience some additional symptoms referable to the bladder, such as frequency, urgency, or nocturia. It can occur across all age groups, although the specific additional symptoms can vary in prevalence depending on patient age. It should be considered in patients who have other chronic pain conditions such as fibromyalgia, chronic fatigue, irritable bowel, and vulvodynia. The cause is still largely not understood, although there are several postulated mechanisms."

McLeod D, Nelson K. 2013. The role of the emergency department in the acute management of chronic or recurrent pain. Australas Emerg Nurs J. 16(1):30-36. "It is evident that the ED is not the ideal setting for managing patients with chronic pain; however, it is the last resort for many who do present, and who will continue to present should their pain persist. It is time to ensure that the ED provides a consistently supportive, cohesive and integrated approach to managing patients with chronic pain syndromes."

McMakin CR, Oschman JL. 2013. Visceral and somatic disorders: tissue softening with frequency-specific microcurrent. J Altern Complement Med. 19(2):170-177. "Frequency-specific microcurrent (FSM) is an emerging technique for treating many health conditions. Pairs of frequencies of microampere-level electrical stimulation are applied to particular places on the skin of a patient via combinations of conductive graphite gloves, moistened towels, or gel electrode patches. A consistent finding is a profound and palpable tissue softening and warming within seconds of applying frequencies appropriate for treating particular conditions. Similar phenomena are often observed with successful acupuncture, cranial-sacral, and other energy-based techniques. This article explores possible mechanisms involved in tissue softening. In the 1970s, neuroscientist and osteopathic researcher Irvin Korr developed a "γ-loop hypothesis" to explain the persistence of increased systemic muscle tone associated with various somatic dysfunctions. This article summarizes how physiologists, neuroscientists, osteopaths, chiropractors, and fascial researchers have expanded on Korr's ideas by exploring various mechanisms by which injury or disease increase local muscle tension or systemic muscle tone. Following on Korr's hypothesis, it is suggested that most patients actually present with elevated muscle tone or tense areas due to prior traumas or other disorders, and that tissue softening indicates that FSM or other methods are affecting the cause of their pathophysiology. The authors believe this concept and the research it has led to will be of interest to a wide range of energetic, bodywork, and movement therapists."

McManimen SL, Jason LA. 2017. Post-exertional malaise in patients with ME and CFS with comorbid fibromyalgia. SRL Neurol Neurosurg. 3(1):22-27. "The secondary diagnosis of FM in addition to ME and CFS appears to amplify the PEM symptomatology and worsen patients' physical functioning. The findings of this study have notable implications on the inclusion of patients with comorbid FM in ME and CFS research studies." Free PMC Article [There was no mention of myofascial trigger points in this study. They have previously been associated with delayed onset muscle soreness after exercise. DJS.]

McMillan AS, Blasberg B. 1994. Pain-pressure threshold in painful jaw muscles following trigger point injection.  J Orofac Pain. 8(4):384-390.  “The pain-pressure threshold was significantly lower in myofascial pain subjects than in control subjects at all recording sites.  Pain-pressure thresholds increased minimally in the masseter after trigger-point injection, whereas the temporal region was relatively unaffected.”  “Although local anesthetic injection acts peripherally at the painful site and centrally where pain is sustained, pain-pressure thresholds were not dramatically increased in myofascial pain subjects, in contrast to controls.  This suggests that in subjects with myofascial pain, there was continued excitability in peripheral tissues and/or central neural areas which may have contributed to the persistence of jaw muscle tenderness.”

McNicholas WT, Bonsignore MR. 2007.  Sleep Apnoea as an independent risk factor for cardiovascular disease: current evidence, basic mechanisms and research priorities.  Eur Respir J. 29(1):156-178.  “Considerable evidence is available in support of an independent association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular disease, which is particularly strong for systemic arterial hypertension and growing for ischaemic heart disease, stroke, heart failure, atrial fibrillation and cardiac sudden death.  The pathogenesis of cardiovascular disease in OSAS is not completely understood but likely to be multifactorial, involving a diverse range of mechanisms including sympathetic nervous system overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism.”

McPartland JM. 2008. Expression of the endocannabinoid system in fibroblasts and myofascial tissues. J Bodyw Mov Ther. 12(2):169-182. The endocannabinoid system affects many systems associated with myofascial formation, and there are many potential tools to modulate these systems, including diet, lifestyle modification and bodywork.

McPartland JM.  2004.  Travell trigger points – molecular and osteopathic perspectives.  JAOA 104(6):244-249.

McPartland JM, Guy GW, Di Marzo V. 2014. Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System. PLoS One. 9(3):e89566. "Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Clinical interventions characterized as "complementary and alternative medicine" also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances-alcohol, tobacco, coffee, cannabis) also modulate the eCB system."

McQuay, H. 1999. Opioids in pain management. Lancet 353(9171):2229-32.

McRae A, Ling EA, Schubert P et al. 1998.  Properties of activated microglia and pharmacologic interference by propentofylline.  Alzheimer Dis Assoc Disord 12 Suppl 2:S15-S20.  This study indicates that propentofylline can down regulate spinal glial cells.  This indicates it may be a useful medication for central sensitization.

McSherry, J. A. 1989. Cognitive impairment after head injury. Am Fam Physician 40(4):186-190. Cognitive impairment is common after head injury, even when the injury has been minor.

McVey C. 1998. Pain in the very preterm baby: 'suffer little children?' Pediatr Rehabil 2(2):47-55. Research indicates that even very preterm infants have the ability to feel pain, and yet they are often not given adequate pain control in spite of procedures that would necessitate pain control in an adult.

McWhorter, J. H. and R. B. Davis. 1998. Cherokee prescriptions for accupressure and massage. NCMJ 59(6):368.

Mease PJ. 2017. Fibromyalgia, a missed comorbidity in spondyloarthritis: prevalence and impact on assessment and treatment. Curr Opin Rheumatol. [Apr 7 Epub ahead of print] This review found that FM is often found in patients with autoimmune conditions. "Disease activity measures with subjective elements are conflated in patients with fibromyalgia and do not reliably assess true inflammatory disease. This needs to be taken into account when evaluating the impact of immunomodulatory therapy." [This is not an indication that FM is autoimmune. Autoimmune conditions themselves are some of many factors that can cause FM central nervous system sensitization, and the FM amplification of symptoms including pain must be taken into consideration when treating patients with multiple conditions. DJS ]

Mease PJ, Farmer MV, Palmer RH et al. 2013. Milnacipran combined with pregabalin in fibromyalgia: a randomized, open-label study evaluating the safety and efficacy of adding milnacipran in patients with incomplete response to pregabalin. Ther Adv Musculoskelet Dis. 5(3):113-126. "In this exploratory, open-label study, adding milnacipran to pregabalin improved global status, pain, and other symptoms in patients with fibromyalgia with an incomplete response to pregabalin treatment." [See: Huskey AM, Thomas CC, Waddell JA. 2013. Occurrence of milnacipran-associated morbilliform rash and serotonin toxicity. Ann Pharmacother. 47(7-8):e32. Look at the peripheral pain generators, and treat those. DJS]

Mediati RD, Vellucci R, Dodaro L. 2014. Pathogenesis and clinical aspects of pain in patients with osteoporosis. Clin Cases Miner Bone Metab. 11(3):169-172. "Bone pain is one of the most frequent kinds of chronic pain, mainly in elderly patients. It causes a significant worsening of functional capacity and deterioration in the quality of life in people affected. Mechanisms of pain in osteoporosis are poorly known and often extrapolated by other pathologies or other experimental model. One of principal causes would be a 'hyper-remodeling' of bone that involves osteoclasts activity and pathological modifications of bone innervation. Several studies show that osteoclasts play a significant role in bone pain etiology. Pain in osteoporosis is mainly nociceptive, if it becomes persistent a sensitization of peripheral and central nervous system can occur, so underlining the transition to a chronic pain syndrome…A balanced and early multimodal pain therapy including opioids as necessary, even in cases of acute pain, improve the functional capacity of patients and helps to prevent neurological alterations that seems to contribute in significant way in causing irreversible pain chronic syndromes." Free PMC Article

Meerlo P, Koehl M, van der Borght K et al. 2002.  Sleep restriction alters the hypothalamic-pituitary-adrenal response to stress.  J Neuroendocrinol 14(5):397-402.

Meeus M, Goubert D, De Backer F et al. 2013. Heart rate variability in patients with fibromyalgia and patients with chronic fatigue syndrome: A systematic review. Semin Arthritis Rheum. [Jul 6 Epub ahead of print]. "FM patients show more HRV (heart rate variability) aberrances and indices of increased sympathetic activity. Increased sympathetic activity is only present in CFS patients at night. Since direct comparisons are lacking and some confounders have to be taken into account, further research is warranted. The role of pain and causality can be subject of further research, as well as therapy studies directed to reduced HRV."

Meeus M , Ickmans K, Struyf F et al. 2014. What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia. Clin Rheumatol. Oct 14. [Epub ahead of print] "Based on the present study, fulfillment of the ME or Canadian criteria did not seem to give a clinically different picture, whereas a diagnosis of comorbid FM selected symptomatically worse and more disabled patients."

Meeus M, Ickmans K, Struyf F et al. 2013. Does Acetaminophen Activate Endogenous Pain Inhibition in Chronic Fatigue Syndrome/Fibromyalgia and Rheumatoid Arthritis? A Double-Blind Randomized Controlled Cross-over Trial. Pain Physician. 16(2):E61-70. "Although enhanced temporal summation (TS) and conditioned pain modulation (CPM), as characteristic for central sensitization, has been proved to be impaired in different chronic pain populations, the exact nature is still unknown....We examined differences in TS and CPM in 2 chronic pain populations, patients with both chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) and patients with rheumatoid arthritis (RA), and in sedentary, healthy controls, and evaluated whether activation of serotonergic descending pathways by acetaminophen improves central pain processing....After intake of acetaminophen, pain thresholds increased slightly in CFS/FM patients, and decreased in the RA and the control group. Temporal summation was reduced in the 3 groups and CPM at the shoulder was better overall, however only statistically significant for the RA group....This is the first study comparing the influence of acetaminophen on central pain processing in healthy controls and patients with CFS/FM and RA. It seems that CFS/FM patients present more central pain processing abnormalities than RA patients, and that acetaminophen may have a limited positive effect on central pain inhibition, but other contributors have to be identified and evaluated."

Meeus M, Nijs J, Hermans L et al. 2013. The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets? Expert Opin Ther Targets. 17(9):1081-1089. "Introduction: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are characterized by persistent pain and fatigue. It is hypothesized that reactive oxygen species (ROS), caused by oxidative and nitrosative stress, by inhibiting mitochondrial function can be involved in muscle pain and central sensitization as typically seen in these patients. Areas covered: The current evidence regarding oxidative and nitrosative stress and mitochondrial dysfunction in CFS and FM is presented in relation to chronic widespread pain. Mitochondrial dysfunction has been shown in leukocytes of CFS patients and in muscle cells of FM patients, which could explain the muscle pain. Additionally, if mitochondrial dysfunction is also present in central neural cells, this could result in lowered ATP pools in neural cells, leading to generalized hypersensitivity and chronic widespread pain. Expert opinion: increased ROS in CFS and FM, resulting in impaired mitochondrial function and reduced ATP in muscle and neural cells, might lead to chronic widespread pain in these patients. Therefore, targeting increased ROS by antioxidants and targeting the mitochondrial biogenesis could offer a solution for the chronic pain in these patients. The role of exercise therapy in restoring mitochondrial dysfunction remains to be explored, and provides important avenues for future research in this area."

Mehling WE, Daubenmier J, Price CJ et al. 2013. Self-reported interoceptive awareness in primary care patients with past or current low back pain. J Pain Res. 6:403-418. "Mind-body interactions play a major role in the prognosis of chronic pain, and mind-body therapies such as meditation, yoga, Tai Chi, and Feldenkrais presumably provide benefits for pain patients. The Multidimensional Assessment of Interoceptive Awareness (MAIA) scales, designed to measure key aspects of mind-body interaction, were developed and validated with individuals practicing mind-body therapies, but have never been used in pain patients. METHODS: We administered the MAIA to primary care patients with past or current low back pain and explored differences in the performance of the MAIA scales between this and the original validation sample. We compared scale means, exploratory item cluster and confirmatory factor analyses, scale-scale correlations, and internal-consistency reliability between the two samples and explored correlations with validity measures. RESULTS: Responses were analyzed from 435 patients, of whom 40% reported current pain. Cross-sectional comparison between the two groups showed marked differences in eight aspects of interoceptive awareness. Factor and cluster analyses generally confirmed the conceptual model with its eight dimensions in a pain population. Correlations with validity measures were in the expected direction. Internal-consistency reliability was good for six of eight MAIA scales. We provided specific suggestions for their further development. CONCLUSION: Self-reported aspects of interoceptive awareness differ between primary care patients with past or current low back pain and mind-body trained individuals, suggesting further research is warranted on the question whether mind-body therapies can alter interoceptive attentional styles with pain. The MAIA may be useful in assessing changes in aspects of interoceptive awareness and in exploring the mechanism of action in trials of mind-body interventions in pain patients."

Mehling WE, Hamel KA, Acree M et al. 2005.  Randomized, controlled trial of breath therapy for patients with chronic low-back pain.  Altern Ther Health Med. 11(4):44-52.  Patients with chronic low back pain improved significantly with breath therapy.  [Although myofascial trigger points were not mentioned in this article, it is very possible that the prevention of paradoxical breathing, a common perpetuating factor in many TrPs that can contribute to or cause low back pain, may have been part of this process. DJS]

Meilinger A, Burger M, Peter HH. 2015. [Heterozygote forms of familial Mediterranean fever can be manifested in adults as myofascial pain syndrome.] Z Rheumatol. [Jan 22 Epub ahead of print.] [Article in German] Familial Mediterranean fever (FMF) is a disease characterized by recurrent fever, serositis, arthritis and unspecific myalgia. It is prevalent among Mediterranean people and has been shown to be associated with mutations in the Mediterranean fever (MEFV) gene…. As heterozygous mutations in MEFV can be associated with only mild inflammatory symptoms, such as arthralgia or chronic fibromyalgic pain, FMF may be underdiagnosed in the current diagnostic work-up of musculoskeletal diseases….This article presents evidence that 9 out of 12 Mediterranean patients with recurrent myofascial pain syndrome and mild inflammation revealed heterozygote mutations in the MEFV gene and 7 of these patients benefitted from treatment with colchicine. As colchicine treatment not only improved the myofascial pain but also prevented FMF-associated amyloidosis and nephropathy, differential diagnosis of fibromyalgia in patients of Mediterranean origin should include FMF and a genetic screening of the MEFV locus.

Meister MR, Shivakumar N, Sutcliffe S et al. 2018. Physical examination techniques for the assessment of pelvic floor myofascial pain: a systematic review. Am J Obstet Gynecol. [Jun 27 Epub ahead of print] "Given the known role of pelvic floor myofascial pain in chronic pelvic pain and link between pelvic floor myofascial pain and lower urinary tract symptoms, physicians should be trained to evaluate for pelvic floor myofascial pain as part of their physical examination in patients presenting with these complaints. Therefore, the development and standardization of a reliable and reproducible examination is needed."

Meister MR, Sutcliffe S, Badu A et al. 2019. Pelvic floor myofascial pain severity and pelvic floor disorder symptom bother: Is there a correlation? Am J Obstet Gynecol. [Jul 15 Epub ahead of print] "Pelvic floor myofascial pain, which is predominantly identified in the muscles of the levator ani and obturator internus, has been observed in women with chronic pelvic pain and other pelvic floor disorder symptoms, and is hypothesized to contribute to their symptoms…. After excluding 79 with an acute urinary tract infection, 833 patients were included in the final analysis. Pelvic floor myofascial pain…was identified in 85.0% of patients: 50.4% rated as severe, 25.0% moderate, and 9.6% mild…. Severity of myofascial pain at several individual pelvic floor sites was also independently correlated with lower urinary tract symptoms, including pain in the lower abdomen (myofascial pain at all sites) and difficulty emptying the bladder (right obturator internus and left levator ani); and with defecatory dysfunction, including sensation of incomplete rectal emptying (pain at all sites combined and the right obturator internus), anal incontinence to flatus (pain at all sites combined), and pain with defecation (pain at all sites combined, and the right obturator internus and left levator ani)…. Given the high prevalence of pelvic floor myofascial pain in these patients and correlation between pain severity and degree of symptom bother, a routine assessment for pelvic floor myofascial pain should be considered for all patients presenting for evaluation of pelvic floor symptoms."

Meister MR, Sutcliffe S, Ghetti C et al. 2018. Development of a standardized, reproducible screening examination for assessment of pelvic floor myofascial pain. Am J Obstet Gynecol. [Dec 7 Epub ahead of print] "Pelvic floor myofascial pain is common, but physical examination methods to assess pelvic floor muscles are poorly defined. We hypothesized that a simple, transvaginal pelvic floor examination could be developed that would be highly reproducible among providers… The final examination protocol begins with examination of the following external sites: bilateral sacroiliac joints, medial edge of the anterior superior iliac spine, and cephalad edge of the pubic symphysis (self-reported pain: yes/no). The internal examination follows with palpation of each muscle group in the center of the muscle belly (MB), then along the length of the muscle proceeding counter-clockwise: right obturator internus (OI), right levator ani (LA), left LA, left OI (pain on a scale of 0-10)…. Our newly-developed, standardized, reproducible examination incorporates assessment of internal and external points to screen for pelvic floor myofascial pain. The examination is straightforward and reproducible allowing for easy use in clinical practice."

Mejuto-Vazquez MJ, Salom-Moreno J, Ortega-Santiago R et al. 2014. Short-term changes in neck pain, widespread pressure pain sensitivity, and cervical range of motion after the application of trigger point dry needling in patients with acute mechanical neck pain: A randomized clinical trial. J Orthop Sports Phys Ther. [Feb 25 Epub ahead of print.] "The results of the current randomized clinical trial suggest that a single session of TrP-DN decreases neck pain intensity and widespread pressure sensitivity, and also increases active cervical range of motion in patients with acute mechanical neck pain. Changes in pain, PPT, and cervical range of motion surpassed their respective minimal detectable change values supporting clinically relevant treatment effects."

Mekhail N, Costandi S, Mehanny DS et al. The impact of tobacco smoking on spinal cord stimulation effectiveness in complex regional pain syndrome patients. Neuromodulation. 2019 Nov 11. [Epub ahead of print] This article from the Cleveland Clinic Foundation [USA] found that tobacco smoking significantly reduced the effectiveness of spinal cord stimulation (SCS) effectiveness for pain relief in complex regional pain syndrome (CRPS) patients.

Melamede RJ. 2005.  Cannabis and tobacco smoke are not equally carcinogenic.  Harm Reduct J. 2(1):21  “Available scientific data that examines the carcinogenic properties of inhaling smoke and its biological consequences suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.”

Melero-Suarez R, Sanchez-Santos JA, Dominguez-Maldonado G. 2018. Evaluation of the analgesic effect of combination therapy on chronic plantar pain through the myofascial trigger points approach. J Am Podiatr Med Assoc. 108(1):27-32. "Closely related pathologic disorders sometimes manifest with the same symptoms, making for a complex differential diagnosis. This is the situation in plantar fasciitis (PF) and myofascial pain syndrome (MPS) with myofascial trigger points (MTPs) in the sole of the foot.... The suggested combination therapy of ultrasound with ICST is clinically significant for reducing plantar pain after 15 treatment sessions, with a 6.5-point reduction in mean PIP and a 4.6-point increase in PPT." [This study compares TrPs with plantar fasciitis, as if they were differential conditions rather than interactive diagnoses or cause and effect. If perpetuating factors are eliminated, and TrPs are eliminated, often plantar fasciitis is eliminated as well. DJS]

Melikoglu M, Melikoglu MA. 2012. The prevalence of fibromyalgia in patients with Behçet's disease and its relation with disease activity. Rheumatol Int. [Sep 28 Epub ahead of print]. "FM is a common and important clinical problem that may represent an additional factor that worsens pain and physical limitations in patients with BD. The higher prevalence of FM in patients with BD seems to be affected by BD itself, rather than its severity." [This study makes an important point. Many conditions have interactive diagnoses, and we need to look for them. DJS]

Mellick GA, Mellick LB. 2003.  Regional head and face pain relief following lower cervical intramuscular anesthetic injection.  Lower cervical intramuscular injection of local anesthetic relieved hyperalgesia and allodynia of the face and scalp associated with migraine headache, as well as associated nausea, photophobia and phonophobia.

Melnick MD, Harrison BR, Park S et al. 2013. A strong interactive link between sensory discriminations and intelligence. Curr Biol. [May 22 Epub ahead of print]. This study linked intelligence (IQ) with the ability to filter out less relevant low-level stimuli. "We conjecture that the ability to suppress irrelevant and rapidly process relevant information fundamentally constrains both sensory discriminations and intelligence, providing an information-processing basis for the observed link." [Fibromyalgia has been shown in research to suppress the normal filtering of information. This contributes to what amounts to constant sensory overload. The central nervous system is overwhelmed by stimuli, keeping the CNS hypersensitized and preoccupied. DJS]

Menant JC, Wong A, Sturnieks DL et al. 2013. Pain and Anxiety Mediate the Relationship Between Dizziness and Falls in Older People. J Am Geriatr Soc. [Jan 25 Epub ahead of print]. "Suffering from neck and back pain and anxiety were mediators of the relationship between dizziness and falls after controlling for poor sensorimotor function and balance. Older people with dizziness might benefit from interventions targeting these mediators such as pain management and cognitive behavioral therapy." [This should include an assessment for TrPs. DJS]

Mendez-Sanchez R, Gonzalez-Iglesias J, Puente-Gonzalez AS et al. 2011. Effects of manual therapy of craniofacial pain in patients with chronic rhinosinusitis: a case series. J Manipulative Physiol Ther. [Oct 27 Epub ahead of print]. This interesting study found that patients with craniofascial pain and "chronic rhinosinusitis" could get relief with manual therapy. This is indicative of possible myofascial trigger point origins of the symptoms. Myofascial TrPs can cause runny nose, craniofascial pain, congestion and other sinus symptoms. DJS]

Meng F, Ge HY, Wang YH et al. 2015. A afferent fibers are involved in the pathology of central changes in the spinal dorsal horn associated with myofascial trigger spots in rats. Exp Brain Res. 233(11):3133-3143. " To confirm the role of A fibers in MTrP-related central changes in the spinal dorsal horn, we studied central sensitization as well as the size of neurons associated with myofascial trigger spots (MTrSs, equivalent to MTrPs in humans) in the biceps femoris muscle of rats and provided some objective morphological evidence. Cholera toxin Β subunit-conjugated horseradish peroxidase was applied to label the MTrS-related neurons, and tetrodotoxin was used to block A fibers specifically. The results showed that in the spinal dorsal horn associated with MTrS, the expression of glutamate receptor (mGluR1α/mGluR5/NMDAR1) increased, while the mean size of MTrS-related neurons was smaller than normal. After blocking A fibers, these changes reversed to some extent. Therefore, we concluded that A fibers participated in the development and maintenance of the central sensitization induced by MTrPs and were related to the mean size of neurons associated with MTrPs in the spinal dorsal horn." [This may be one of the first steps proving that small fiber neuropathy is due to trigger points. DJS]

Mengshoel AM. 2007.  What is important to ease the life with fibromyalgia syndrome – review of qualitative studies.  J Musculoskel Pain 15 (Supp 13):55 item 97.  [Myopain 2007 Poster]  “The patients considered that the following were important for easing their lives: 1. Getting a diagnosis for validating illness and helping to focus their further search of information about explanations and management possibilities; 2. Learning strategies to cope with FMS by not overdoing.  This implies accepting the situation, adapting to the boundaries set by illness, and adjusting to everyday life situations and social obligations; 3. Support and recognition from health professionals, family and others.”

Mengshoel, A. M., Forre O., and H. B. Komnaes. 1990. Muscle strength and aerobic capacity in primary fibromyalgia. Clin Exp Rheumatol 8(5):475-479.

Mengshoel AM, Heggen K. 2004. Recovery from fibromyalgia – previous patients’ own experiences.  Disabil Rehabil 26(1):46-53.  This small study of 5 women found that they had been able to “...alter life goals and everyday obligations...”, while “...maintaining a social role they considered to be consistent with their self-image.”  It suggests that some patients with FMS may become symptom free if their perpetuating factors can be controlled.

Mengshoel AM, Sim J, Ahlsen B et al. 2017. Diagnostic experience of patients with fibromyalgia - A meta-ethnography. Chronic Illn. [Jan 1 Epub ahead of print] "Years were normally spent consulting specialists in an attempt to confirm the reality of symptoms and make sense of the illness. Great relief was felt at finally achieving the fibromyalgia syndrome diagnosis. However, relief waned when therapies proved ineffective. Health professionals and others questioned whether individuals were genuinely ill, that the illness had a psychological nature, and whether they were doing their best to recover. The diagnosis did not provide a meaningful explanation of individuals' suffering and had limited power to legitimate illness. Patients felt blamed for their failure to recover, threatening their personal credibility and moral identity. Conclusion The fibromyalgia syndrome diagnosis has limitations in validating and making sense of patients' illness experiences and in providing social legitimation of their illness. Social relationships are strained during the diagnostic process and in the course of ineffective therapies." [There were no assessments for co-existing myofascial trigger points. When therapies fail to consider the causes of the FM central sensitization and other symptoms such as unrestorative sleep, patients and care providers feel helpless and hopeless. Diagnosis itself is not enough. DJS]

Mense S. 2011. [Differences between myofascial trigger points and tender points.] Schmerz. 25(1):93-104 [German]. "The article describes and compares the characteristics of myofascial trigger points (MTrPs) of the myofascial pain syndrome and the tender points (TePs) of the fibromyalgia syndrome. Many statements are hypothetical, because not all aspects of the disorders have been clarified in solid studies. Signs and symptoms of MTrPs: (1) palpable nodule, often located close to the muscle belly, (2) often single, (3) allodynia and hyperalgesia at the MTrP, (4) referral of the MTrP pain, (5) normal pain sensitivity outside the MTrPs, (6) local twitch response, (7) local contracture in biopsy material, (8) peripheral mechanism probable. Signs and symptoms of TePs: (1) no palpable nodule, (2) location often close to the muscle attachments, (3) multiple by definition, (4) allodynia and hyperalgesia also outside the TePs, (5) enhanced pain under psychic stress, (6) unspecific histological changes in biopsy material, (7) central nervous mechanism probable. The multitude of differences speaks against a common aetiology and pathophysiology."

Mense S. 2010. How do muscle lesions such as latent and active trigger points influence central nociceptive neurons? J Musculoskel Pain. 18(4):348-353. "Spontaneous pain is mainly due to ongoing activity in nociceptive neurons in the spinal cord. Allodynia and hyperalgesia can be explained by a sensitization of central nociceptive neurons (central sensitization). One mechanism of central sensitization is the release of substance P together with glutamate from presynaptic terminals of nociceptive fibers from muscle. Other steps of sensitization are the opening of N-methyl-d-aspartate channels on postsynaptic neurons and the de novo synthesis of ion channels. The current concept of pain referral assumes that the efficacy of synaptic connections of central dorsal horn neurons can change under the influence of a nociceptive input. Thus, ineffective synaptic connections can become effective. Pain referral appears to reflect the formation of new effective central nervous connections." "Myofascial TrPs are not merely a peripheral phenomenon, the input from TrPs leads to hyperexcitability of central neurons that manifests itself in allodynia, hyperalgesia, and pain referral. These central changes are mainly based on an increase in the synaptic efficacy of central connections induced by nociceptive input." "Allodynia (pain evoked by stimuli that are not normally painful) and hyperalgesia (stronger than usual pain evoked by a painful stimulus) can be explained by a sensitization of central nociceptive neurons (central sensitization)." "One mechanism of central sensitization is the release of the neuromodulator SP together with glutamate from presynaptic terminals of nociceptive fibers from muscle." [This article explains how TrPs can cause central sensitization states such as FM, and that glial cell activation is a critical part of this process. DJS]

Mense S. 2004. Neurobiological basis for the use of botulinum toxin in pain therapy. J Neurol 251(Suppl 1):1/1-1/7.  Botulinum toxin interferes with the release of acetylcholine from cholinergic nerve endings, and thus interferes with the probable mechanism of TrP formation. Botulinum toxin interferes with this process, thus acting upon the pain cause, rather than just offering symptomatic relief.

Mense S, Hoheisel U. 2004.  Central nervous sequelae of local muscle pain.  J Musculoskeletal Pain 12(3/4):101-109.  This excellent overview explains how the body and mind work to handle acute pain, and how some of these very changes can backfire in some patients to promote chronic pain.  There are mechanisms in place to prevent this, but there are many variables in both series of processes.  Research in chronic pain mechanisms, especially involving glial cells, offer hope for answers in the near future.

Mense S. 2004.  Neurobiological basis for the use of botulinum toxin in pain therapy.  J Neurol. 251 Suppl 1:I1-7.  “During chronic pain conditions, at all levels massive neuroplastic changes take place that lead to rewiring of connections and structural alterations in the nuclei of the nociceptive pathways.  In chronic pain patients the neuroanatomy of pain probably differs from that of healthy people.”

Mense S. 2004.  [Mechanisms of transition from acute to chronic muscle pain] [German] Orthopade 33(5):525-532.  “Norepinephrine is known to increase cases of chronic pain, and is a stimulant of muscle nociceptors.  If BoNT inhibits the release of these transmitters, it could be analgesic in cases of sympathetically maintained pain including the complex regional pain syndrome.”

Mense S. 2003.  What is different about muscle pain?  Schmertz 17(6):459-463.  This article calls attention to the fact that most of the studies on pain are done on pain arising from the skin, and yet it is deeper pains, from fascia, muscle, tendon and joint that are more clinically significant.  Research indicates that the mechanisms of cutaneous pain and pain originating elsewhere are different, and suggest dysfunction in descending pain-modulating pathways could lead to the type of pain associated with fibromyalgia. [German]

Mense S. 2003.  The pathogenesis of muscle pain.  Curr Pain Headache Rep 7(6):419-415. This excellent article brings out many fine points that are often missed in the study of central sensitization and muscle pain.  Low pH can sensitize receptors, and a low local pH is common in ischemia and inflammation and other conditions and can be part of the neuroplastic changes leading to central sensitization, causing spontaneous pain and hyperalgesia and allodynia. This paper also brings attention to the fact that once central sensitization has taken place, it takes time to normalize the body.  This does not mean it is impossible to do so, just that the patient and the clinicians must try to restore the body balances carefully. All perpetuating factors must be addressed and the body given a chance to reestablish balance.  There is no quick fix.  It takes time.

Mense S. 1999.  [Neurobiological basis of muscle pain] [German] Schmerz. 13(1):3-17.  “The central sensitization can explain the hyperalgesia and spread of pain in patients.  Chronic spontaneous muscle pain, however, appears to be due to a lack of NO [nitric oxide].  The final step in the transition from acute to chronic pain involves structural changes that perpetuate the functional changes.  In rat experiments employing nerve lesions or muscle inflammation, such morphological changes become apparent within a few hours after the lesion.”  [Research into the development of chronic pain has the potential to lead to new understanding and new therapies and medications to prevent and treat it. DJS] 

Mense, S., Simons, D.G., Hoheisel, U., et al. 2003.  Lesions of rat skeletal muscle following local block of acetylcholinesterase and neuromuscular stimulation.  J Appl Physiol [***epub ahead of print].  “The results support the assumption that a dysfunctional endplate exhibiting increased release of [acetylcholine] may be the starting point for regional abnormal contractions which are thought to be essential for the formation of myofascial trigger points.”

Menzies V, Taylor AG, Bourguignon C. 2006.  Effects of guided imagery on outcomes of pain, functional status, and self-efficacy in persons diagnosed with fibromyalgia.  J Altern Complement Med. 12(1):23-30.  “This study demonstrated the effectiveness of guided imagery in improving functional status and sense of self-efficacy for managing pain and other symptoms of FM.  However, participants’ reports of pain did not change.”

Meran S, Martin J, Luo DD et al. 2013. Interleukin-1beta induces hyaluronan and CD44-dependent cell protrusions that facilitate fibroblast-monocyte binding. Am J Path. 182(6):2223-2240. This study concerns the possible mechanisms behind persistent inflammation as a determinant of progressive tissue fibrosis. These authors found that if they stimulated fibroblasts, the most common type of connective tissue cell, with interleukin 1-beta, the hyaluronic acid within the fibroblast relocates to the outer cell membrane, forming protrusions. They conclude that their study suggests that the interleukin beta-1 generated hyaluronic acid (hyaluronan) is involved in fibroblast immune activation, which may sequester monocytes in the inflamed tissues, resulting in a state of chronic inflammation. [This research meshes well with the studies we did on geloid masses inpatients with FM and CMP, and indicates that patients with FM and CMP may need to be very careful using any product with hyaluronic acid. HA is a component in many cosmetics, body lotions, and anti-aging formulas. DJS]

Meresh ES, Artin H, Joyce C et al. 2019. Obstructive sleep apnea co-morbidity in patients with fibromyalgia: a single-center retrospective analysis and literature review. Open Access Rheumatol. Apr 29;11:103-109. "We conducted a site-wide review of patients from 2012-2016 to identify FM patients diagnosed with OSA... Charts were reviewed in patients aged 18 and above from 2012-2016 using ICD codes from a clinical data repository. Intersection of patients with a diagnosis of FM and OSA in clinics of psychiatry, sleep, rheumatology, and other outpatient clinics was compared. Polysomnography order patterns for FM patients were investigated.... Co-morbidity was highest in the sleep clinic (85.8%) compared to psychiatry (42.0%), rheumatology (18.7%), and other outpatient clinics (3.6%) (p<0.001). In the rheumatology and other outpatient clinics, 93.5% and 96% of patients respectively, had no polysomnography ordered (emphasis DJS).... Our analysis suggests that there could be a correlation between FM and OSA, and referral to sleep studies is recommended in the management of patients with FM. The varying prevalence of FM patients with co-morbid OSA in sleep clinics when compared to other outpatient clinics suggests a discrepancy in the identification of FM patients with OSA. When properly screened, OSA co-morbidity has the potential to be higher in other outpatient clinics."[Polysomnography is useful for patients with chronic pain and fatigue; not only to discover sleep apnea. Sleep architecture dysfunction and co-existing conditions may be revealed. DJS]

Merkes M. 2010. Mindfulness-based stress reduction for people with chronic diseases. Aust J Prim Health. 16(3):200-210. "Chronic diseases are associated with a range of unwelcome psychological and physical consequences. Participation in an MBSR (mindfulness-based stress reduction) program is likely to result in coping better with symptoms, improved overall well-being and quality of life, and enhanced health outcomes. As an adjunct to standard care, MBSR has potential for much wider application in Australian primary care settings."

Mermi O, Atmaca M. 2016. [Duloxetine-Induced Hypertension: A Case Report]. Turk Psikiyatri Derg. 27(1):67-69. [Free Article in Turkish] "Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is used for diabetic neuropathic pain and fibromyalgia as well as major depressive disorder. Serotonin-norepinephrine reuptake inhibitors may lead to increased blood pressure via their noradrenergic effects in addition to their cardiovascular side effects. In this paper, we report a case with increased blood pressure after the initiation of duloxetine that recovered by discontinuation of the medication."

Merriwether EN, Frey-Law LA, Rakel BA et al. 2018. Physical activity is related to function and fatigue but not pain in women with fibromyalgia: baseline analyses from the Fibromyalgia Activity Study with TENS (FAST). Arthritis Res Ther. 20(1):199. "Lifestyle physical activity is not equally related to all aspects of fibromyalgia symptomology. Lifestyle physical activity levels have the strongest correlations with function, physical quality of life, and movement fatigue in women with fibromyalgia. No relationships between lifestyle physical activity and pain, pain sensitivity, or psychological constructs were observed. These data suggest that physical activity levels are more likely to affect function and fatigue, but have negligible relationships with pain and pain-related psychological constructs, in women with fibromyalgia."

Mesaroli G, Ruskin D, Campbell F et al. Clinical Features of Pediatric Complex Regional Pain Syndrome: A 5-Year Retrospective Chart Review. Clin J Pain. 2019 Sep 4. [Epub ahead of print] "Complex regional pain syndrome (CRPS) is a painful condition of a limb characterized by a constellation of symptoms. Little is known about the clinical features of pediatric CRPS, with fewer than a dozen studies published to date. The aim of this study was to explore the clinical course of pediatric CRPS, with emphasis on clinical features and disease outcomes. A secondary aim was to discern differences in clinical features of pediatric CRPS with and without related movement disorders, and between children who had a favorable and unfavorable outcome…. In this cohort, pediatric CRPS was most common in females around the age of 12, usually in the lower extremity, and most experienced a favorable outcome. Further research is needed to better understand the prognosis and relapse rate of pediatric CRPS."

Mesci E, Mesci N, Doğruöz Karatekin B, et al. Can early fatigue in leg muscles after exercise cause postural instability in women with fibromyalgia? J Musculoskelet Neuronal Interact. 2023 Sep 1;23(3):338-345. "Lower limb muscle fatigue occurs earlier in FMS patients than in healthy individuals and exacerbates postural stability problems. This indicates the importance of planning tailored exercise programs for these patients.

Mesplie N, Kerautret J, Leoni-Mesplie S et al. 2010. [Central toxic keratopathy and fibromyalgia: a case report.] J Fr Ophtalmol. [Jul 29 Epub ahead of print]. [French] "Diffuse lamellar keratitis (DLK) is a sterile inflammation after laser in situ keratomileusis. Central toxic keratopathy is characterized by noninflammatory central corneal opacification with a significant hyperopic shift. The cause of central toxic keratopathy is unknown. Fibromyalgia is a widespread, chronic pain disorder that includes a complex constellation of somatic and emotional symptoms. Patients often complain of dry eye sensations. Recent studies have highlighted a reduced corneal sensitivity in patients with fibromyalgia. There could be a relation between fibromyalgia, diffuse lamellar keratitis, and central toxic keratopathy. Some precautions may be used before LASIK in patients with fibromyalgia."

Metin Okmen B, Okmen K, Altan L. 2017. Comparison of the efficiency of ultrasound-guided injections of the rhomboid major and trapezius muscles in myofascial pain syndrome: A prospective randomized controlled double-blind study. J Ultrasound Med. [Oct 19 Epub ahead of print.] "We think that US-guided deep injection of the rhomboid major muscle was more effective than superficial injection of the trapezius muscle for pain, disability, and quality of life in patients with myofascial pain syndrome."

Metyas S, Chen CL, Yeter K et al. 2018. Low Dose Naltrexone in the treatment of fibromyalgia. Curr Rheumatol Rev. 14(2):177-180. "A significant number of fibromyalgia patients do not respond adequately to the current drugs (pregabalin, milnacipran, duloxetine) approved for fibromyalgia treatment by the Food and Drug Administration (FDA). Thus, there is still a need for adjunctive therapies. Naltrexone is an opioid receptor antagonist used to treat alcohol and opioid dependence. It is hypothesized that low dose naltrexone causes transient blockade of opioid receptors centrally resulting in a rebound of endorphin function which may attenuate pain in fibromyalgia. Treatment with low dose naltrexone may be an effective, highly tolerable and inexpensive treatment for fibromyalgia."

Metyas S1, Rezk T, Arkfeld D, Leptich T. 2016. The Inflammatory Fibromyalgia. Curr Rheumatol Rev. [Sep 19 Epub ahead of print.] "Recent studies have described cytokines, inflammatory markers, sleep disorders, hyperalgesia, cognitive dysfunction, serum leptin levels and other inflammatory indicators as potential markers for iFM. This article will; 1) review the inflammatory markers and abnormal levels of other laboratory indicators that can help to identify the subgroup of patients that fall into the new category of Inflammatory Fibromyalgia [1-5] and 2) review all completed trials that were focused on treating this new category of disease. Through this review it is hoped that and further understanding of the complexity of the etiology of fibromyalgia can be explored". [This may be something new and real, or may be only another misunderstanding. These authors did not check for coexisting conditions, including myofascial trigger points, nor show understanding of the many different causes of cognitive dysfunction, sleep disorders, cytokine activation, hyperalgesia, etc. that may be in play. DJS]

Meyer HP. 2002.  Myofascial pain syndrome and its suggested role in the pathogenesis and treatment of fibromyalgia syndrome. Curr Pain Headache Rep 6(4):274-83. Failure on the part of care providers to recognize myofascial pain from trigger points often leads to costly and unnecessary tests and  procedures. This failure to diagnose can result in harm to the patients.

Meyer UA, Zanger UM. 1997.  Molecular mechanisms of genetic polymorphisms of drug metabolism.  Annu Rev Pharmacol Toxicol. 37:269-296.  Yet another study of how genetics can influence metabolism of drugs.  Some patients are ultra-rapid metabolizers, and some are slow metabolizers.

Mian AN, Chaabo K, Wajed J et al. 2016. Rheumatoid arthritis patients with fibromyalgic clinical features have significantly less synovitis as defined by power Doppler ultrasound. BMC Musculoskelet Disord. 17(1):404. RA patients who also have symptoms of fibromyalgia may have fewer inflamed joints and less synovial fluid accumulation but higher disease activity scores. "This has implications for the identification and management of these patients who may not respond to conventional therapy and hence be more suitable for alternative approaches to treatment". Free PMC Article

Michael DM, Warren GL. 2007.  Effect of trigger point treatment on muscle activation patterns in hip extension movement.  J Musculoskel Pain 15 (Supp 13):32 item 54.  [Myopain 2007 Poster]  “Treatment of TrPs may improve lumbopelvic function.”

Michels T. 2020. Peripheral neuropathic pain and pain related to complex regional pain syndrome with and without fixed dystonia - Efficient therapeutic approach with local anesthetics. Local Reg Anesth. Jan 31;13:11-16. "Peripheral neuropathic pain" (PNP) as well as the complex regional pain syndrome (CRPS), also known as "reflex sympathetic dystrophy", or "Sudeck dystrophy", all of them have a poor prognosis. The numerous therapeutic offers are rarely accompanied by convincing success over a long duration of time. Even worse is the prognosis of a fixed dystonia which may develop in the extremities of PNP or CRPS patients. In literature a few cases are reported in which the often unbearable pain of those patients with or without a disabling dystonia disappeared immediately after the injection of local anesthetics (LAs) into the scars of a preceding trauma. This review evaluates publications concerning the neuropathological characteristics of fixed dystonia in PNP/CRPS patients and the electrophysiological processes of scar neuromas. The results of these evaluations support the understanding of the therapeutic successes and their immediate results reported above by the injection of LAs into triggering scars." [Might there be scar TrPs involved in some CRPS pain? No one has yet researched possible scar TrPs involved with the injections mentioned here, but other sources have reported that TrP injections are helpful for the "pain of CRPS". DJS]

Miernik M, Wieckiewicz M, Paradowska A. 2012. Massage therapy in myofascial TMD pain management. Adv Clin Exp Med. 21(5):681-685. Myofascial pain located in the area of the head is a very common disease of the stomatognathic system. The fact that the mechanism of its development is very complex may cause a variety of problems in diagnosis and therapy. Patients diagnosed with this type of affliction usually need a variety of different therapies. Massage therapy can be a significant method of treatment of myofascial pain. That kind of therapy is clinically useful as it improves the subjective and objective health status of the patient and is easy to follow. The aim of this paper is to show the physiological effect and different massage techniques applied in myofascial pain treatment. The authors would also like to present the protocol for dealing with patients who demand that kind of therapy for masseter and temporal muscles.

Mifflin KA, Kerr BJ. 2013. The transition from acute to chronic pain: understanding how different biological systems interact. Can J Anaesth. [Nov 26 Epub ahead of print]. "Although pain is an adaptive sensory experience necessary to prevent further bodily harm, the transition from acute to chronic pain is not adaptive and results in the development of a chronic clinical condition. How this transition occurs has been the focus of intense study for some time. The focus of the current review is on changes in neuronal plasticity as well as the role of immune cells and glia in the development of chronic pain from acute tissue injury and pain….Our understanding of the complex pathways that mediate the transition from acute to chronic pain continues to increase. Work in this area has already revealed the complex interactions between the nervous and immune system that result in both peripheral and central sensitization, essential components to the development of chronic pain. Taken together, a thorough characterization of the cellular mechanisms that generate chronic pain states is essential for the development of new therapies and treatments."

Miholic J, Hoffman M, Hoist JJ et al. 2007.  Gastric emptying of glucose solution and associated plasma concentrations of GLP-1, GIP, and PYY before and after fundoplication.  Surg Endosc. [Jan 2 Epub ahead of print]  Fundoplication is implicated as a perpetuating factor in hypoglycemia, which is itself a perpetuating factor for FMS and CMP.

Mikkelsson M, Latikka P, Kautiainen H et al. 1992.  Muscle and bone pressure pain threshold and pain tolerance in fibromyalgia patients and controls.  Arch Phys Med Rehabil. 73(9):814-818.  “…patients with primary fibromyalgia have a generalized amplification of pain sensitivity, a sign that might be useful in the diagnosis of fibromyalgia.”

Miller, C. S. 1999. Are we on the threshold of a new theory of disease? Toxicant-induced loss of tolerance and its relationship to addiction and abdiction. Toxicol Ind Health 15(3-4):284-94.

Miller G. 2005.  The dark side of glia.  Science 308:778-781.  Glial cell activation is a promising target for chronic pain medication.  Glial cells direct neurons to release neurotransmitters, and regulate synaptic traffic.  This involves them in memory and learning processes.  Glia may be involved in the origin of MS, neuropathic pain, chronic pain, and some types of seizures.  Medications already available may work on overexcited glia, but they haven’t been tested for this yet.  Now that more researchers are aware of the pathological properties of some types of activated glia, new avenues for treatment will be developed.

Miller GE, Chen E, Parker KJ. 2011. Psychological stress in childhood and susceptibility to the chronic diseases of aging: moving towards a model of behavioral and biological mechanisms. Psychol Bull. 137(6):959-997. People who are exposed to major psychological stressors in early life have a susceptibility to chronic diseases associated with aging. The altered responses to the endocrine and autonomic systems can amplify the proinflammatory environment, adding to the tendency toward developing chronic diseases.

Miller JS, Rodriguez-Saona L, Hackshaw KV. 2020. Metabolomics in central sensitivity syndromes. Metabolites. Apr 24;10(4). "Central sensitization syndromes are a collection of frequently painful disorders that contribute to decreased quality of life and increased risk of opiate abuse. Although these disorders cause significant morbidity, they frequently lack reliable diagnostic tests. As such, technologies that can identify key moieties in central sensitization disorders may contribute to the identification of novel therapeutic targets and more precise treatment options. The analysis of small molecules in biological samples through metabolomics has improved greatly and may be the technology needed to identify key moieties in difficult to diagnose diseases. In this review, we discuss the current state of metabolomics as it relates to central sensitization disorders…. The majority of metabolomic studies addressing a CSS found significantly altered metabolites that allowed for differentiation of CSS patients from healthy controls. Therefore, the published literature overwhelmingly supports the use of metabolomics in CSS. Further research into these altered metabolites and their respective metabolic pathways may provide more reliable and effective therapeutics for these syndromes. [This may be of importance in FM, as conditions such as insulin resistance and thyroid resistance are frequent perpetuating factors and often missed. DJS]

Miller MB, Chan WS, Boissoneault J et al. 2017. Dynamic daily associations between insomnia symptoms and alcohol use in adults with chronic pain. J Sleep Res. [Sep 22 Epub ahead of print] "Individuals with chronic pain are at risk for sleep disruption and heavy alcohol use, yet the daily associations between these behaviours are not well characterized….To our knowledge, these data provide the first evidence that alcohol use negatively affects insomnia symptoms up to 2 days post-consumption in patients reporting symptoms of insomnia and chronic pain. Findings suggest that one drink will have minimal impact on sleep, but heavier drinking (e.g., four-five drinks) may have a clinically significant impact (16-25 min. increase in sleep-onset latency)."

Miller MB, Chan WS, Curtis AF et al. 2018. Pain intensity as a moderator of the association between opioid use and insomnia symptoms among adults with chronic pain. Sleep Med. 52:98-102 "This study aimed to determine if pain intensity moderates the association between opioid use and insomnia symptoms among adults with comorbid symptoms of insomnia and chronic widespread pain.... Stronger pain intensity was associated with longer self-reported WASO (wake after sleep onset) and worse sleep quality, independent of opioid use. Conversely, opioid use was associated with longer time in bed, independent of pain intensity. Opioid use and pain intensity interacted in the prediction of SOL (sleep onset latency), such that opioid use (vs. non-use) was associated with longer SOL in the context of mild but not moderate to severe pain intensity.... Opioid use was associated with more difficulty falling asleep among adults with chronic pain; however, this cross-sectional effect was only significant among those reporting lower pain intensity. Authors speculate that this effect is masked among those with severe pain because the pain-related sleep debt they acquire throughout the night then facilitates sleep onset the next day."

Miller PL, Ernst AA. 2004.  Sex differences in analgesia: a randomized trial of mu versus kappa opioid agonists.  South Med J 97(1):35-41.  Kappa opioids such as butorphanol may work better for pain in women than mu opioids such as morphine. 

Minehira K., Tappy L. 2002.  Dietary and lifestyle interventions in the management of the metabolic syndrome: present and future perspective.  Eur J Clin Nutr 56(12):1264-9.  “Future research, in particular the genetic basis of the metabolic syndrome and the interorgan interactions responsible for insulin resistance, is needed to improve therapeutic strategies for the metabolic syndrome.”

Minerbi A, Fitzcharles MA. 2020. Gut microbiome: pertinence in fibromyalgia. Clin Exp Rheumatol. 38 Suppl 123(1):99-104. "The composition of the gut bacterial community is altered in individuals with FM, with an altered abundance of a small subset of bacterial species. Some of these species, either with increased or decreased abundance in patients, have established metabolic activity which could have pertinence in the expression of FM symptoms. The putative mechanisms which could allow these bacterial species to affect pain, fatigue, mood and other symptoms include the entry of short-chain-fatty-acids, bile acids, neurotransmitters and bacterial antigens into the host circulation."

Minerbi A, Gonzalez E, Brereton N et al. 2022. Altered serum bile acid profile in fibromyalgia is associated with specific gut microbiome changes and symptom severity. Pain. May 19. Online ahead of print. "Alterations in the relative abundance of several bacterial species known to metabolize bile acids were observed in women with fibromyalgia, accompanied by significant alterations in the serum concentration of secondary bile acids, including a marked depletion of α-muricholic acid…. Serum α-muricholic acid was highly correlated with symptom severity, including pain intensity and fatigue. …. The changes observed in the composition of the gut microbiota and the concentration of circulating secondary bile acids seem congruent with the phenotype of increased nociception, and are quantitatively correlated with symptom severity. This is a first demonstration of circulating bile acid alteration in individuals with fibromyalgia, potentially secondary to upstream gut microbiome alterations."

Minerbi A, Gonzalez E, Brereton NJB et al. 2019. Altered microbiome composition in individuals with fibromyalgia. Pain. [Jun 18 Epub ahead of print] "When comparing FM patients to unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa. Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM. In line with observed alteration in butyrate metabolising species, targeted serum metabolite analysis verified differences in the serum levels of butyrate and propionate in FM patients…. To the best of our knowledge, this is the first demonstration of gut microbiome alteration in non-visceral pain."

Minerbi A, Vulfsons S. 2018. Challenging the Cinderella Hypothesis: A new model for the role of the motor unit recruitment pattern in the pathogenesis of myofascial pain syndrome in postural muscles. Rambam Maimonides Med J. 24:1-8. "The motor unit relaxation/contraction time ratio decreases with elevated muscle loads and with decreased total muscle strength.... In a model of a postural muscle, in which motor units are recruited in rotation, common predisposing factors of myofascial pain, such as increased muscle load and decreased muscle force, lead to shortened motor unit relaxation periods."

Minhas D, Clauw DJ. 2021. Pain mechanisms in patients with rheumatic diseases. Rheum Dis Clin North Am. May;47(2):133-148. "Patients with rheumatic diseases often have mixed pain states, with varying degrees of nociceptive, neuropathic, and nociplastic mechanisms, which exist on a continuum. When individuals with any chronic pain have a nociplastic component to their symptoms, they are less likely to respond to treatments (eg, injections, surgery, biologics, and opioids) that work better for acute or purely nociceptive pain."

Minhas D, Murphy A, Clauw DJ. Fibromyalgia and centralized pain in the rheumatoid arthritis patient. Curr Opin Rheumatol. 2023 Feb 13. Online ahead of print. "Central pain mechanisms that may be contributing to pain in RA are common and should be distinguished from pain directly arising from peripheral inflammation."

Minich DM, Bland JS. 2007.  Acid-alkaline balance: role in chronic disease and detoxification.  Altern Ther Health Med. 13(4):62-65.  “The increasing dietary acid load in the contemporary diet can lead to a disruption in acid-alkaline homeostasis in various body compartments and eventually result in chronic disease through repeated borrowing of the body’s alkaline reserves.”

Mira E, Martanez MP, Sanchez AI et al. 2011. When is pain related to emotional distress and daily functioning in fibromyalgia syndrome? The mediating roles of self-efficacy and sleep quality. Br J Health Psychol. 16(4):799-814. "Sleep dysfunction is importantly related to FM symptoms and deserves more attention in both research and clinical practice. Our results suggest that, in addition to the usual treatment of FM, improving sleep could optimize the current management of the syndrome." [This agrees with other research that have shown that polysomnography (sleep studies) are a necessary part of all fibromyalgia work-ups when fatigue or non-restorative sleep is part of the symptoms. If the patient is tired when they wake up, it's time to find out why. DJS]

Miranda, A. F., R. J. Boegman, R. J. Beninger and K. Jhamandas. 1997. Protection against quinolinic acid-mediated excitotoxicity in nigrostriatal dopaminergic neurons by endogenous kynurenic acid. Neuroscience 78(4):967-975.

Miro E, Lupianez J, Hita E et al. 2011. Attentional deficits in fibromyalgia and its relationships with pain, emotional distress and sleep dysfunction complaints. Psychol Health. 3:1-16. "Cognitive complaints are common among subject with fibromyalgia (FM). Yet, few studies have been able to document these deficits with cognitive tasks. A main limitation of existing studies is that attention has been broadly defined and the tasks used to measure attention are not designed to cover all the main components of the attentional system. Research on attention has identified three primary functions of attention, known as alerting, orienting and executive functioning. This study used the attentional network test-interactions task to explore whether and which of the three attentional networks are altered in FM. Results showed that FM patients have impaired executive control (greater interference), reduced vigilance (slower overall reaction time) and greater alertness (higher reduction in errors after a warning cue). Vigilance and alertness showed several relations with depression, anxiety and sleep quality. Sleep dysfunction was a significant predictor for alertness, whereas there were no significant predictors for vigilance. These findings highlight that the treatment of sleep difficulties in FM patients may help with some of their cognitive complaints."

Miro E, Martinez MP, Sanchez AI et al. 2014. Men and women with fibromyalgia: Relation between attentional function and clinical symptoms. Br J Health Psychol. [Dec 29 Epub ahead of print.] "Control men were faster than control women, but FM eliminated sex differences. In addition, attention deficit was associated with worse daily functioning in women but not in men with FM. Emotional distress and sleep disruption seemed to contribute differently to these cognitive alterations in both sexes….Therapy strategies aimed at reducing emotional distress and sleep disruption are likely to improve cognitive function by enhancing vigilance. Therapies aimed at reducing emotional distress seem to improve attentional function more in women than in men; those aimed at improving sleep quality are likely to reduce a vigilance/alertness deficit in women and executive problems in men."

Mirzaei A, Zabihiyeganeh M, Jahed SA et al. 2018. Effects of vitamin D optimization on quality of life of patients with fibromyalgia: A randomized controlled trial. Med J Islam Repub Iran. 5;32:29. "This study suggests that vitamin D supplementation has significant therapeutic benefits in the management of FMS, especially in pain reduction of patients with fibromyalgia. According to our results, a combination of vitamin D supplements and a conventional antidepressant (Trazadone), when given to vitamin D-deficient fibromyalgia patients, could significantly improve both physical and psychological symptoms."

Misirlioglu TO, Akgun K, Palamar D et al. 2015. Piriformis syndrome: comparison of the effectiveness of local anesthetic and corticosteroid injections: a double-blinded, randomized controlled study. Pain Physician. 18(2):163-171. The object of this study was to "… investigate the differences between local anesthetic (LA) and LA + corticosteroid (CS) injections in the treatment of PS (piriformis syndrome)." The study found no difference in outcome with the addition of steroids. [Steroids are myotoxic. This is yet another study showing no benefit to the use of steroids in trigger point injection. DJS] Free Article

Mist SD, Firestone KA, Jones KD. 2013. Complementary and alternative exercise for fibromyalgia: a meta-analysis. J Pain Res. 6:247-260. "Complementary and alternative medicine includes a number of exercise modalities, such as tai chi, qigong, yoga, and a variety of lesser-known movement therapies. A meta-analysis of the current literature was conducted estimating the effect size of the different modalities, study quality and bias, and adverse events. The level of research has been moderately weak to date, but most studies report a medium-to-high effect size in pain reduction. Given the lack of adverse events, there is little risk in recommending these modalities as a critical component in a multimodal treatment plan, which is often required for fibromyalgia management."

Miyawaki S, Tanimoto Y, Araki Y et al. 2004.  Relationships among nocturnal jaw muscle acitivites, decreased esophageal pH, and sleep positions.  Am J Orthod Dentofacial Orthop 126(5):615-619.  GERD episodes that occur while sleeping on the back can trigger jaw muscle activities, including bruxism.

Modell, W. J. Travell and J Kraus et al. 1952. Relief of pain by ethyl chloride spray. NY State Med 52;1550-1558.

Mody R, Bolge SC, Kannan H et al. 2009.  Effects of gastro-esophageal reflux disease on sleep and outcomes.  Clin Gastroenterol Hepatol. [Apr 15 Epub ahead of print].  “Nighttime GERD symptoms are associated with interruption of sleep induction and maintenance and result in considerable economic burden and reduction in HRQOL (health-related quality of life).”

Moeller-Bertram T, Strigo IA, Simmons AN et al. 2014. Evidence for Acute Central Sensitization to Prolonged Experimental Pain in Posttraumatic Stress Disorder. Pain Med. [Apr 16 Epub ahead of print.] "Post-traumatic stress disorder (PTSD) and pain have a well-documented high comorbidity; however, the underlying mechanisms of this comorbidity are currently poorly understood." This study found: "… a significantly higher degree of acute central sensitization in individuals with PTSD. Increased acute central sensitization may underlie increased vulnerability for developing pain-related conditions following combat trauma."

Moeschler SM, Pollard EM, Pingree MJ et al. 2021. Ultrasound-guided transversus abdominis plane block vs. trigger point injections for chronic abdominal wall pain: a randomized clinical trial. Pain. Jan 5. Online ahead of print. "The main finding of this randomized clinical trial is that adults with chronic AWP (abdominal wall pain) who received a TPI (trigger point injection) reported significantly lower pain scores at month 3 follow-up compared to patients who received a TAP (transversus abdominis plane) block."

Mogil, J. S., S. P. Richards, L. A. O’Toole, M. L. Helms, S. R. Mitchell, B. Kest and J. K. Belknap. 1997. Identification of a sex-specific quantitative trait locus mediating nonopioid stress-induced analgesia in female mice. J Neurosci 17(20):7995-8002.

Mohamadi M, Rojhani-Shirazi Z, Asadsangabi R et al. 2020. Proton magnetic resonance spectroscopy to detect correlations between clinical symptoms and brain metabolite levels in patients with tension-type headache. J Biomed Phys Eng. Oct 1;10(5):583-588. "Proton magnetic resonance spectroscopy (1HMRS) is a noninvasive method to quantify pain. A 1HMRS spectrum is a group of peaks at different radiofrequencies, showing proton nuclei in various chemical environments. These MR spectra provide information about metabolite concentrations, and make MRS a useful procedure to monitor metabolic fluctuations due to disease, and to track the efficacy of treatment. … There was a negative correlation between trigger point count and choline/creatine (Cho/Cr) ratio in the primary somatosensory cortex …. There were no correlations between other clinical symptoms of TTH and concentrations of brain metabolites…. Patients with more trigger points had a lower Cho/Cr ratio, which may indicate alterations in brain metabolic activity."

Mohamed DA, Kamal RM, Gaber MM, et al. 2021. Combined effects of extracorporeal shockwave therapy and integrated neuromuscular inhibition on myofascial trigger points of upper trapezius: A randomized controlled trial. Ann Rehabil Med. Aug;45(4):284-293. "Combined treatment with ESWT and INI for treating myofascial trigger points in the upper trapezius is more effective than using only one of the two approaches in terms of clinical, functional, and neurophysiological aspects".

Mohammad A, Carey JJ, Storan E et al. 2012. High Prevalence of Fibromyalgia in Patients with HFE-related Hereditary Hemochromatosis. J Clin Gastroenterol. [Nov 21 Epub ahead of print]. "This study reveals a high prevalence of FMS (43%) among subjects with HFE-related hemochromatosis. Prospective studies are needed to better understand the risk factors for FMS in such patients."

Mohammad A, Carey JJ, Storan E et al. 2012. Prevalence of fibromyalgia among patients with chronic hepatitis C infection: relationship to viral characteristics and quality of life. J Clin Gastroenterol. 46(5):407-412. "This study reveals a high prevalence of FMS (57%) among subjects with chronic HCV infection, one third of whom reported some degree of functional impairment. Recognition and management of this condition in such patients will help improve their quality of life."

Mohan A, Alexandra SJ, Johnson CV et al. 2018. Effect of distress on transient network dynamics and topological equilibrium in phantom sound perception. Prog Neuropsychopharmacol Biol Psychiatry. 84(Pt A):79-92. This is a comparative study of healthy individuals and individuals with high levels of distress due to ringing of the ears (tinnitus). The authors found that tinnitus could cause a significant loss of freedom and a feeling of "small-worldness" that can be misunderstood. "In addition, this is correlated with the amount of distress only in the high distress tinnitus group, suggesting a catastrophic breakdown of the brain's resilience. Distress not only accompanies tinnitus, but other disorders such as somatic disorders, fibromyalgia, post-traumatic stress disorder, etc. Since the current study focuses on a disorder-general distress symptom, the methods and results of the current study have a wide application in different neuropathologies."

Mohandas M, Sharan D, Ranganathan R et al. 2014. Co-morbidities of myofascial neck pain among information technology professionals. Ann Occ Env Med. 26:21. This study was done with 71% males using laptop and/or desktop computers at occupational health clinics in India. Neck pain was the most common symptom, followed by low back, shoulder, and arm pain. Neck pain among females was significantly higher than in males. Myofascial pain syndrome was the commonest musculoskeletal disorder leading to pain in males and females. Thoracic Outlet Syndrome, Fibromyalgia, and eye strain were also common.

Mohanty AF, Helmer DA, Muthukutty A et al. 2016. Fibromyalgia syndrome care of Iraq- and Afghanistan-deployed veterans in Veterans Health Administration. J Rehabil Res Dev. 53(1):45-58. "Little is known regarding fibromyalgia syndrome (FMS) care among Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND) Veterans….We found that 1% of Veterans had at least 2 FMS diagnoses (International Classification of Diseases-9th Revision-Clinical Modification code 729.1) or at least 1 FMS diagnosis by rheumatology. Veterans with (vs without) FMS were more likely to be female, older, Hispanic, and never/currently married. Combined primary, mental health, and rheumatology care was associated with at least 2 opioid prescriptions (RR [95% CI] for males 2.2 ….and females 2.8…. Also, combined care was associated with at least 2 nonopioid pain-related prescriptions, a practice supported by evidence-based clinical practice guidelines. In tandem, these results provide mixed evidence of benefit of combined care for FMS."

Mohanty AF, Muthukutty A, Carter ME et al. 2015. Chronic multisymptom illness among female veterans deployed to Iraq and Afghanistan. Med Care. 53(4 Suppl 1):S143-148. "CMI-related diagnoses were more prevalent among female OEF/OIF/OND Veterans compared with all female Veterans who currently access VHA. Future studies of the role of mental health diagnoses as confounders or mediators of the association of OEF/OIF/OND deployment and CMI are warranted. These and other factors associated with CMI may provide a basis for enhanced screening to facilitate recognition of these conditions. Further work should evaluate models of care and healthcare utilization related to CMI in female Veterans."

Mohapatra G, Dachet F, Coleman LJ, et al. Identification of unique genomic signatures in patients with fibromyalgia and chronic pain. 2024. Sci Rep. 2024 Feb 17;14(1):3949. The result of this study indicates that FM is a heterogeneous and complex disease. Further elucidation of these pathways will lead to the development of accurate diagnostic markers, and effective therapeutic options for fibromyalgia.

Moldofsky H. 2010.  Rheumatic manifestations of sleep disorders.  Curr Opin Rheumatol. 22(1):59-63.  “The determination of how disordered sleep affects musculoskeletal pain, fatigue, mood, and behavior is important in the assessment and management of patients with rheumatic illness.  The high prevalence of obstructive sleep apnea and restless legs syndromes requires more research to determine whether treatments of these sleep disorders will benefit the symptoms of rheumatic diseases.”  [This lovely paper by the master of sleep disorders is of vital importance.  The impact of unrestorative sleep cannot be overestimated, and there are many components to sleep disturbances.  Unrestorative sleep must be considered not only as a perpetuating factor but as an interactive diagnosis with many other illnesses, including those associated with musculoskeletal pain.  Thank you, Dr. Moldofsky.]

Moldofsky H. 2009.  The significance of dysfunctions of the sleeping/waking brain to the pathogenesis and treatment of fibromyalgia syndrome.  Rheum Dis Clin North Am. 35(2):275-283.  “This article reviews how functional disturbances of the sleeping-waking brain are involved in pathogenesis of the widespread pain, unrefreshing sleep, fatigue, and impaired quality of life of patients who have fibromyalgia syndrome.”  One of the most common perpetuating factors for FM is lack of restorative sleep.  There are pharmaceutical and physical agents that can help pain and  fatigue while regaining restorative sleep.

Moldofsky H. 2007.  The assessment and significance of the sleep/waking brain in patients with chronic widespread musculoskeletal pain and fatigue syndromes.  J Musculoskel Pain 15 (Supp 13):4 item 5.  [Myopain 2007 Poster]  “Psychophysiological studies demonstrate that total, partial and rapid eye movement [REM] sleep deprivations decrease pain threshold.  Pain stimuli disturb sleep, and non-painful stimuli [e.g. noise] that disrupt sleep [e.g. slow wave sleep] cause unrefreshing sleep, myalgia and fatigue.”  “In clinical studies of FMS and chronic fatigue syndrome, unrefreshing sleep is associated with frequent periodic electroencephalogram arousals from sleep, i.e. the cyclical alternating pattern, sleep apneas, and periodic limb movements.”  “Preliminary studies of novel treatments that aim to facilitate restorative sleep suggest a rationale for better management of FMS and related illnesses.”  [This information indicates that many sleep dysfunctions are interactive with FM and other disorders.]


Moldofsky, H. 2002. Management of sleep disorders in fibromyalgia.  Rheum Dis Clin North Am 28(2):353-65. "In summary, the treatment of patients with FM requires a proper assessment of the reason for the unrefreshing sleep, which is an important component of the FM syndrome."

Moldofsky, H. 1995. Sleep and the immune system. Int J Immunopharmacol 17(8):649-654.

Moldofsky H, Harris HW, Archambault WT et al. 2011. Effects of Bedtime Very Low Dose Cyclobenzaprine on Symptoms and Sleep Physiology in Patients with Fibromyalgia Syndrome: A Double-blind Randomized Placebo-controlled Study. J Rheumatol. [Sep 1 Epub ahead of print]. "Bedtime VLD( very low dose) CBP (cyclobenzaprine) treatment improved core FM symptoms."

Moldofsky H, Inhaber NH, Guinta DR et al. 2010. Effects of Sodium Oxybate on Sleep Physiology and Sleep/Wake-related Symptoms in Patients with Fibromyalgia Syndrome: A Double-blind, Randomized, Placebo-controlled Study. J Rheumatol. [Aug 3 Epub ahead of print]. "This large cohort of patients with FM demonstrated that SXB treatment improved EEG sleep physiology and sleep-related FM symptoms." [Sodium oxybate does restore deep sleep, the area of sleep wherein neurotransmitters, hormones and other informational substances are balanced. It is most unfortunate for FM patient that the fear diversion to illegal use has caused the FDA to deny its use for FM patients. DJS]

Moldwin RM, Fariello JY. 2013. Myofascial trigger points of the pelvic floor; Associations with urological pain syndromes and treatment strategies including injection therapy. Curr Urol Rep. 14(5):409-417. "Myofascial trigger points (MTrP), or muscle 'contraction knots', of the pelvic floor may be identified in as many as 85% of patients suffering from urological, colorectal and gynecological pelvic pain syndromes; and can be responsible for some, if not all, symptoms related to these syndromes. Identification and conservative treatment of MTrPs in these populations has often been associated with impressive clinical improvements. In refractory cases, more 'aggressive' therapy with varied trigger point needling techniques, including dry needling, anesthetic injections, or botulinum toxin A injections m, may be used, in combination with conservative therapies."

Molina F, Del Moral ML, La Rubia M et al. 2019. Are patients with fibromyalgia in a prothrombotic state? Biol Res Nurs. Jan 17:1099800418824716. "The aim of this study was to investigate thrombosis-related parameters (blood coagulation parameters, platelet indices, red blood cell [RBC] count, and inflammatory markers) in patients with fibromyalgia (FM)… We carried out a case-control study with 35 women with FM and 12 age-matched healthy volunteers to analyze fibrinogen levels, prothrombin time, cephaline time, platelet count, platelet distribution width (PDW), mean platelet volume (MPV), RBC count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR)…. Elevated platelet and RBC counts, PDW values, and fibrinogen levels as well as decreased prothrombin time are all indicative of a prothrombotic state in FM patients, which may be enhanced by an increased inflammatory tone. This prothrombotic state may increase the risk of thrombosis-related cardiovascular disease in patients with FM."

Molina J, Amaro E Jr, da Rocha LGS et al. 2017. Functional resonance magnetic imaging (fMRI) in adolescents with idiopathic musculoskeletal pain: a paradigm of experimental pain. Pediatr Rheumatol Online J. 15(1):81. "Adolescents with idiopathic musculoskeletal pain (IMP) tend to request higher brain function in cognitive-emotional areas when interpreting unpredictable sensory-perceptual situations. Therefore, it is assumed that this difference in pain processing in adolescents with IMP make the subjective experience of pain something more intense and unpleasant." Free Article

Molina J, Dos Santos FH, Terreri MT et al. 2012. Sleep, stress, neurocognitive profile and health-related quality of life in adolescents with idiopathic musculoskeletal pain. Clinics (Sao Paulo). 67(10):1139-1144. Adolescents with idiopathic musculoskeletal pain did not exhibit cognitive impairments. However, adolescents with idiopathic musculoskeletal pain did experience intermediate to advanced psychological distress and lower health-related quality of life, which may increase their risk of cognitive dysfunction in the future.

Moller-Levet CS, Archer SN, Bucca G et al. 2013. Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcritome. Proc Natl Acad Sci USA. 110(12):E1132-1141. "…insufficient sleep affects the human blood transcriptome, disrupts its circadian regulation, and intensifies the effects of acute total sleep deprivation. The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the interrelatedness of sleep homeostasis, circadian rhythmicity, and metabolism." The change from 8 hours a night to 6 hours a night of sleep for even one week can cause drastic genetic effects. After one week of the 6 hour a night sleep regimen, tests of the formerly healthy subjects showed that 711 of their genes had changed, including ones that regulate the immune system.

Molnar DS, Flett G, Sadava SW et al. 2012. Perfectionism and health functioning in women with fibromyalgia. J Psychosom Res. 73(4):295-300. "Collectively, these findings clarify that overall levels of perfectionism are not elevated among women with fibromyalgia (emphasis mine DJS), but those women who are exceptionally high in levels of self-oriented perfectionism or high in socially prescribed perfectionism are particularly likely to suffer lower health functioning. These results suggest that perfectionism should be specifically assessed and targeted for intervention among women with fibromyalgia and there should be a particular emphasis on the pressure to meet perceived or actual expectations imposed on the self."

Molto A, Dougados M. 2018. Comorbidities in spondyloarthritis, including psoriatic arthritis. Best Pract Res Clin Rheumatol. 32(3):390-400. "Comorbidities in spondyloarthritis (SpA) including psoriatic arthritis have to be differentiated to the concept of clinical features of SpA (e.g., uveitis, psoriasis, and inflammatory bowel disease). In addition to atherosclerosis-related cardiovascular diseases, the most frequent comorbidities in SpA are osteoporosis, fibromyalgia, and depression. Moreover, the current available drug therapies (e.g., NSAIDs, corticosteroids, and biologics) might increase the risk of some comorbidities such as infections and gastrointestinal disorders. Awareness about these comorbidities is crucial to improve their screening and management. For this purpose, any systematic periodical review should integrate a program (ideally internationally standardized) focused on comorbidities."

Momi SK, Fabiane SM, Lachance G et al. 2015. Neuropathic pain as part of chronic widespread pain: environmental and genetic influences. Pain. [Jun 24 Epub ahead of print.] "Chronic widespread pain (CWP) has complex aetiology and forms part of the fibromyalgia syndrome. Recent evidence suggests a higher frequency of neuropathic pain features in those with CWP than previously thought….. This is the first study to provide formal heritability estimates for neuropathic pain in CWP. The findings suggest that at least some of the genetic factors underlying the development of neuropathic pain and CWP are the same."

Monga, T. N., G. Tan, H. J. Ostermann, U. Monga and M. Grabois. 1998. Sexuality and sexual adjustment of patients with chronic pain. Disabil Rehabil 20(9):317-29.

Monsivais D, Engebretson JC. 2012. I'm Just Not That Sick: Pain Medication and Identity in Mexican American Women with Chronic Pain. J Holist Nurs. [Jun 19 Epub ahead of print]. "To describe the beliefs and attitudes about self-identity and pain medication in a sample of Mexican American women with chronic pain living in the El Paso, Texas, area. The findings are drawn from a larger qualitative study of 15 women describing the expression and communication of chronic pain symptoms, pain-related cultural beliefs, decision making, and treatment preferences of chronic pain....A shared central theme was controlling the use of pain medications to control perceived negative associations with pain medication. The negative associations resulted in women rejecting use of medication to preserve their legitimate identity. This perception can be destructive and can lead to poor pain control....Providing patients with anticipatory guidance about common barriers to taking pain medication may allow medication use consistent with improved pain control.

Montanez-Aguilera FJ, Valtuena-Gimeno N, Pecos-Martin D et al. 2010. Changes in a patient with neck pain after application of ischemic compression as a trigger point therapy. J Back Musculoskelet Rehabil. 23(2):101-104. This article describes the improvement of one patient who had neck pain for at least four months. After one session of ischemic compression on the left trapezius, range of motion increased, electromyography improved and pain decreased.

Montenegro ML, Braz CA, Rosa-E-Silva JC et al. 2015. Anesthetic injection versus ischemic compression for the pain relief of abdominal wall trigger points in women with chronic pelvic pain. BMC Anesthesiol. 15:175. "Chronic pelvic pain is a common condition among women, and 10 to 30 % of causes originate from the abdominal wall, and are associated with trigger points. … Lidocaine injection seems to be better for reducing the severity of chronic pelvic pain secondary to abdominal wall trigger points compared to ischemic compression via physical therapy." Free PMC Article

Montenegro ML, Gomide LB, Mateus-Vasconcelos EL et al.  2009. Abdominal myofascial pain syndrome must be considered in the differential diagnosis of chronic pelvic pain.  Eur J Obstet Gynecol Reprod Biol. [Jul 21 Epub ahead of print].  “Abdominal myofascial pain syndrome is a highly prevalent disease associated with CPP (chronic pelvic pain), and because of this physicians should get used to making a precise and early diagnosis in order to avoid additional and unnecessary investigation.”  [Yet another study showing that myofascial trigger points are extremely common and that much pain could be saved by myofascial trigger point assessment.  This requires adequate training for care providers in the diagnosis of TrPs, which would save enormous amounts of money and avoid many procedures and testing in the long term.  DJS]

Monteso-Curto P, Cubi-Guillen MT, Navarro ANL, et al. 2021. Family perceptions and experiences of living with patients with fibromyalgia syndrome. Disabil Rehabil. Jul 7;1-8. "Three categories of family perceptions of FMS emerged: (1) manifestations of FMS; (2) FMS is regarded as a psychological problem; (3) FMS interferes with traditional gender roles. Three categories of family members' experience of living with FMS patients were identified: (1) emotional concerns and exhaustion; (2) overprotective family members; and (3) escape coping... Because family members tend to dismiss fibromyalgia as a psychological problem for which ignoring or distracting the patient is the best approach to coping, rehabilitation programs should give family members education and training to develop the ability to better understand fibromyalgia and reduce stereotypes about the condition."

Montoro CI, Duschek S, de Guevara CM et al. 2016. Patterns of cerebral blood flow modulation during painful stimulation in fibromyalgia: A transcranial Doppler sonography study. Pain Med. [May 31 Epub ahead of print.] "The results demonstrate that acute pain processing is associated with a complex pattern of CBF (cerebral blood flow modulation), where FMS patients exhibited alterations in all phases of the response. The aberrances may be ascribed to psychophysiological phenomena, including central nervous nociceptive sensitization and protective-defensive reflex mechanisms. The anticipatory CBF response in patients may relate to various cognitive, emotional, and behavioral mechanisms involved in pain chronification."

Montoro CI, Duschek S, Munoz Ladron de Guevara C et al. 2014. Aberrant Cerebral Blood Flow Responses during Cognition: Implications for the Understanding of Cognitive Deficits in Fibromyalgia. Neuropsychology. [Aug 25 Epub ahead of print.] "There is ample evidence for cognitive deficits in fibromyalgia syndrome (FMS). The present study investigated cerebral blood flow responses during arithmetic processing in FMS patients and its relationship with performance. …. Cognitive impairment in FMS is associated with alterations in cerebral blood flow responses during cognitive processing. These results suggest a potential physiological pathway through which psychosocial and clinical factors may affect cognition."

Montoro CI, Duschek S, Schuepbach D et al. 2018. Cerebral blood flow variability in fibromyalgia syndrome: Relationships with emotional, clinical and functional variables. PLoS One. 13(9):e0204267. "This study analyzed variability in cerebral blood flow velocity (CBFV) and its association with emotional, clinical and functional variables and medication use in fibromyalgia syndrome (FMS).... Lower CBFV variability in the LF and HF ranges were observed in FMS, suggesting impaired coordination of cerebral regulatory systems. CBFV variability was differentially associated with clinical variables as a function of time-scale, with short-term variability being related to better clinical outcomes. CBFV variability analysis may be a promising tool to characterize FMS pathology and it impact on facets of HRQoL (health-related quality of life)."

Montoya P, Larbig W, Braun C et al. 2004.  Influence of social support and emotional context on pain processing and magnetic brain responses in fibromyalgia.  Arthritis Rheum. 50(12):4035-4044.  “…social support through the presence of a significant other can influence pain processing at the subjective-behavioral level as well as the central nervous system level.”

Montserrat-de la Paz S, Garcia-Gimenez MD, Quilez AM et al. 2018. Ginger rhizome enhances the anti-inflammatory and anti-nociceptive effects of paracetamol in an experimental mouse model of fibromyalgia. Inflammopharmacology. [Feb 8 Epub ahead of print]. "These findings provide evidence that the daily consumption of GR (ginger rhizome) enhances the anti-nociceptive effect of APAP (acetaminophen) in mice, improves other cognitive disturbances associated with chronic pain, and reduces the inflammatory state generated in an experimental FMS model."

Moon SJ, Kang KY, Kwok SK et al 2018. Differences in quality of life determinants according to the presence of fibromyalgia in middle-aged female patients with systemic lupus erythematosus: a multicenter, cross-sectional, single-ethnicity cohort. Int J Rheum Dis. 21(6):1173-1184. "Poor sleep quality is the common independent risk factor for poor HRQoL (health-related quality of life) in both middle-aged SLE (systemic lupus erythematosus) patients with fibromyalgia and without fibromyalgia. Sleep quality improvement may improve HRQoL in female SLE patients, even in those without fibromyalgia."

Moon YE, Kim SH, Seok H et al. 2019. Efficacy of Topical Vibratory Stimulation for Reducing Pain during Trigger Point Injection to the Gastrocnemius: A Randomized Controlled Trial. Arch Phys Med Rehabil. [Mar 26 Epub ahead of print] "Topical vibratory stimulation significantly decreased pain during TPI of the gastrocnemius.

Moore MK. 2004.  Upper crossed syndrome and its relationship to cervicogenic headache. J Manipulative Physiol Ther. 27(6):414-420.  A patient with one-sided headache radiating to the eye was found to have bilateral myofascial trigger points in the pectoralis major, levator scapulae, upper trapezius and supraspinatus muscles.  Appropriate therapy relieved the headache and its perpetuating factors.

Moore RA, Straube S, Paine J et al. 2010. Fibromyalgia: Moderate and substantial pain intensity reduction predicts improvement in other outcomes and substantial quality of life gain.Pain. [Mar 25 Epub ahead of print]. “Chronic pain is associated with a range of other problems, including disturbed sleep, depression, anxiety, fatigue, reduced quality of life, and an inability to work or socialize. We investigated whether good symptom control of pain (using definitions of moderate and substantial benefit) is associated with improvement in other symptoms. Individual patient data from four randomized trials in fibromyalgia (2575 patients) lasting 8-14weeks were used to calculate percentage pain reduction for each completing patient (1858), divided into one of five groups according to pain reduction, irrespective of treatment: substantial benefit - 50% pain reduction; moderate - 30% to <50%; minimal - 15% to <30%; marginal - 0% to <15%; worse - <0% (increased pain intensity). We then calculated change from baseline to end of trial for measures of fatigue, function, sleep, depression, anxiety, ability to work, general health status, and quality-adjusted life year (QALY) gain over a 12-month period. Substantial and moderate pain intensity reductions were associated with statistically significant reduction from baseline by end of trial in all measures, with values by trial end at or approaching normative values. Substantial pain intensity reduction resulted in 0.11 QALYs gained, and moderate pain intensity reduction in 0.07 QALYs gained over a 12-month period. Substantial and moderate pain intensity reduction predicts broad beneficial outcomes and improved quality of life that do not occur without pain relief. Pain intensity reduction is a simple and effective predictor of which patients should continue treatment, and which should discontinue and try an alternative therapy."

Moore T, Sodhi N, Kalsi A et al. 2019. A nationwide comparative analysis of medical complications in fibromyalgia patients following total knee arthroplasty (TKA). Ann Transl Med. Feb;7(4):64. "As the number of fibromyalgia patients under orthopaedic care is expected to rise, it is imperative that the TKA outcomes of these patients are tracked in order to provide optimal patient care. This study identified fibromyalgia as a risk factor for a number of medical complications following TKA. Orthopaedic surgeons must be aware of the potential for poor TKA outcomes among these patients and should provide them with appropriate medical care and pre-operative guidance."

Moraska AF, Hickner RC, Kohrt WM et al. 2012. Changes in blood flow and cellular metabolism at a myofascial trigger point with trigger point release (ischemic compression): a proof-of-principle pilot study. Arch Phys Med Rehabil. [Sep 10 Epub ahead of print]. "Identifying physiological constituents of MTrPs following intervention is an important step toward understanding pathophysiology and resolution of myofascial pain. The present study forwards that aim by showing proof-of-concept for collection of interstitial fluid from an MTrP before and after intervention can be accomplished using microdialysis, thus providing methodological insight toward treatment mechanism and pain resolution. Of the biomarkers measured in this study, lactate may be the most relevant for detection and treatment of abnormalities in the MTrP."

Moraska AF, Hickner RC, Rzasa-Lynn R et al. 2018. Increase in lactate without change in nutritive blood flow or glucose at active trigger points following massage: A randomized clinical trial. Arch Phys Med Rehabil. [Aug 6 Epub ahead of print] Twenty-five adults (18-49 years old) from the general population with episodic or chronic tension-type headache and an active MTrP in the upper trapezius muscle were given either a single trigger point release (TRP) massage or sham ultrasound (US) treatment at an active MTrP in the upper trapezius muscle. "Microdialysis was used to continuously sample interstitial fluid from the MTrP before, during, and for 60 min following intervention.... The primary outcome measure was nutritive blood flow within the MTrP as measured by microdialysis ethanol clearance; secondary measures included dialysate glucose, dialysate lactate, and subject discomfort with the procedures. Pressure-pain threshold (PPT) was determined to assess treatment effectiveness.... TPR massage of an active MTrP affected anaerobic metabolism as represented by an increase in dialysate lactate without change in nutritive blood flow or dialysate glucose. "

Moraska AF, Schmiege SJ, Mann JD et al. 2017. Responsiveness of myofascial trigger points to single and multiple trigger point release massages: A randomized, placebo controlled trial. Am J Phys Med Rehabil. [Feb 28 Epub ahead of print.] "This study aimed to assess the effects of single and multiple massage treatments on pressure-pain threshold (PPT) at myofascial trigger points (MTrPs) in people with myofascial pain syndrome expressed as tension-type headache…. Single and multiple massage applications increase PPT at MTrPs. The pain threshold of MTrPs have a great capacity to increase; even after multiple massage treatments additional gain in PPT was observed."

Moraska AF, Stenerson L, Butryn N et al. 2014. Myofascial trigger point-focused head and neck massage for recurrent tension-type headache: A randomized, placebo-controlled clinical trial. Clin J Pain. 2014 Oct 17. [Epub ahead of print] "(1) MTrPs (myofascial trigger points) are important components in the treatment of TTH (tension-type headaches), and (2) TTH, like other chronic conditions, is responsive to placebo. Clinical trials on headache that do not include a placebo group are at risk for overestimating the specific contribution from the active intervention."

Morf S, Amann-Vesti B, Forster A et al. 2005.  Microcirculation abnormalities in patients with fibromyalgia – measured by capillary microscopy and laser fluxmetry.  Arthritis Res Ther. 7(2):R209-216.  “...the peripheral blood flow in FM patients was much less than in healthy controls but did not differ from that of SSc [systemic scleroderma] patients.  The data suggest that functional disturbances of microcirculation are present in FM patients and that morphological abnormalities may also influence their microcirculation.”

Morgan BC, Deyle GD, Petersen EJ et al. 2019. Dry needling in the management of patients meeting clinical diagnostic criteria for subacromial pain syndrome: A case series. Int J Sports Phys Ther. 14(4):637-654. "This case series provides insight into the observed short- and intermediate-term effects of dry needling combined with exercise for SAPS. Additionally, it discusses the framework of clinical reasoning when applying this intervention. The results are encouraging for dry needling as an adjunct to exercise for treating patients with SAPS." Free Article

Moriarty KJ, Dawson AM. 1982. Functional abdominal pain: further evidence that whole gut is affected. Br Med J (Clin Res Ed). 284(6330):1670-1672. "The distribution and referral of abdominal pain in 21 patients with functional abdominal pain were investigated by performing balloon distension of the ileum, proximal jejunum, second part of the duodenum, and distal oesophagus. Pain was perceived not just in classically described sites but throughout the abdomen and was referred to several unusual extra-abdominal sites. The presenting pain was reproduced by this technique in 14 patients, in three of whom it was also reproduced by colonoscopic distension. This study emphasises the protean presentation of functional abdominal pain and demonstrates the existence of potentially tender "trigger" areas for the production of abdominal pain in the proximal as well as the distal gut." Free Article

Moriatis Wolf J, Cameron KL, Owens BD. 2011. Impact of joint laxity and hypermobility on the musculoskeletal system. J Am Acad Orthop Surg. 19(8):463-471. "Excessive joint laxity, or hypermobility, is a common finding of clinical importance in the management of musculoskeletal conditions. Hypermobility is common in young patients and in general is associated with an increased incidence of musculoskeletal injury. Hypermobility has been implicated in ankle sprains, anterior cruciate ligament injury, shoulder instability, and osteoarthritis of the hand. Patients with hypermobility and musculoskeletal injuries often seek care for diffuse musculoskeletal pain and injuries with no specific inciting event. Orthopaedic surgeons and other healthcare providers should be aware of the underlying relationship between hypermobility and musculoskeletal injury to avoid unnecessary diagnostic tests and inappropriate management. Prolonged therapy and general conditioning are typically required, with special emphasis on improving strength and proprioception to address symptoms and prevent future injury. Orthopaedic surgeons must recognize the implications of joint mobility syndromes in the management and rehabilitation of several musculoskeletal injuries and orthopaedic disorders."

Morikawa Y, Takamoto K, Nishimaru H et al. 2017. Compression at myofascial trigger point on chronic neck pain provides pain relief through the prefrontal cortex and autonomic nervous system: A pilot study. Front Neurosci. 11:186. "Along with previous studies indicating a role for sympathetic activity in the exacerbation of chronic pain, the present results suggest that MTrP compression in the neck region alters the activity of the autonomic nervous system via the prefrontal cortex to reduce subjective pain." Free Article

Morillas-Arques P, Rodriguez-Lopez CM, Molina-Barea R et al. 2010. Trazodone for the treatment of fibromyalgia: an open-label, 12-week study. BMC Musculoskel Disord. 10;11:204. "Trazodone markedly improved sleep quality, with large effect sizes in total PSQI (Pittsburgh Sleep Quality Index) score as well on sleep quality, sleep duration and sleep efficiency. Significant improvement, although with moderate effect sizes, were also observed in total FIQ scores, anxiety and depression scores...and pain interference with daily activities. Unexpectedly, the most frequent and severe side effect associated with trazodone in our sample was tachycardia, which was reported by 14 (21.2%) patients....In doses higher than those usually prescribed as hypnotic, the utility of trazodone in fibromyalgia management surpasses its hypnotic activity. However, the emergence of tachycardia should be closely monitored."

Morimoto D, Isu T, Kim K et al. 2016. [Non-specific back pain due to superior cluneal nerve entrapment neuropathy treated with neurolysis: A case report]. No Shinkei Geka. 44(2):155-160. [Article in Japanese] "A 43-year-old man with a 10-year history of low back pain (LBP) had been conservatively treated elsewhere with medications for non-specific back pain. He presented to our institute with LBP and difficulty in standing up, sitting down, and sitting for prolonged periods. His Numerical Rating Scale score, due to LBP, was 8 out of 10. He had numbness on the lateral aspect of his left thigh. A lumbar radiography and magnetic resonance imaging studies revealed mild degenerative changes and mild canal stenosis in the lumbar spine. Palpation over the left posterior superior iliac crest, 8 cm from the midline over the iliac crest, revealed severe tenderness. A superior cluneal nerve (SCN) block performed at the trigger point in both the buttocks resulted in complete pain abatement and disappearance of the radiating pain. Therefore, we diagnosed SCN entrapment neuropathy (SCNE). However, the pain reappeared a few days later and subsequent treatments failed to relieve it; therefore, we decided to perform surgery. The SCN penetrates the thoracolumbar fascia through an orifice just before crossing over the iliac crest. We opened the orifice with microscissors in a distal to rostral direction along the SCN and released the entrapped nerve. After surgery, the symptoms were relieved and the patient experienced no recurrence in the last 4 years after the treatment. SCNE should be considered as a causative factor of LBP, and its treatment using minimally invasive surgery yields excellent clinical outcome." Sometimes, myofascial nerve entrapment may require surgery to resolve.

Moriwaki K, Shiroyama K, Yasuda M et al. Reversible tactile hypoesthesia associated with myofascial trigger points: a pilot study on prevalence and clinical implications. Pain Rep. 2019 Jul 15;4(4):e772. "Tactile hypoesthesia observed in patients with myofascial pain syndrome (MPS) is sometimes reversible when pain is relieved by trigger point injections (TPIs). We aimed to investigate the prevalence of such reversible hypoesthesia during TPI therapy and topographical relations between areas of tactile hypoesthesia and myofascial trigger points (MTrP) in patients with MPS….Our results indicate a relatively high prevalence of reversible tactile hypoesthesia in patients with MPS. Mapping of tactile hypoesthetic areas seems clinically useful for detecting MTrP. In addition, treating MTrP with TPI may be important for distinguishing tactile hypoesthesia associated with MPS from that with neuropathic pain."

Moriwaki K, Uesugi F, Kusunoki S et al. 2000.  [Pain management for patients with cancer—current problems in a pain clinic] Masui. 49(6):680-685. [Japanese]  A large proportion of cancer patients were given some amount of pain relief by treatment of trigger points and/or nerve block.  Assessment of cancer and other chronic pain patients for co-existing trigger points would seem a basic part of standard adequate medical care.

Morjaria JB, Lakshminarayana UB, Liu-Shiu-Cheong P et al. 2014. Pneumothorax: a tale of pain or spontaneity. Ther Adv Chronic Dis. 5(6):269-273. Of these two case studies, one of them considers a mastectomy patient with multiple conditions that had pneumothorax secondary to trigger point injection. That case did not require surgical procedure, and the other did. Free Article

Mork P, Nilsson J, Loras H et al. 2013. Heart rate variability in fibromyalgia patients and healthy controls during non-REM and REM sleep: a case-control study. Scand J Rheumatol. [Feb 20 Epub ahead of print]. "RMSSD (root mean square successive difference), indicative of parasympathetic predominance, is attenuated in FM patients compared to HCs (healthy controls) during N2 (non-REM stage 2) sleep and REM sleep. This difference was not present for the HF component. HRV (heart rate variability) during sleep in FM patients is moderately and positively associated with sleep quality and moderately and negatively associated with neck/shoulder pain."

Moroni, F. 1999. Tryptophan metabolism and brain function: focus on kynurenine and other indole metabolites. Eur J Pharmacol 375(1-3):87-100.

Morris, C. E. 1999. Chiropractic rehabilitation if a patient with S1 radiculopathy associated with a large lumbar disk herniation. J Manupulative Physiol Ther 22(1):38-44.

Morris G, Anderson G, Berk M et al. 2013. Coenzyme Q10 depletion in medical and neuropsychiatric disorders: potential repercussions and therapeutic implications. Mol Neurobiol. [Jun 13 Epub ahead of print]. "Coenzyme Q10 (CoQ10) is an antioxidant, a membrane stabilizer, and a vital cofactor in the mitochondrial electron transport chain, enabling the generation of adenosine triphosphate. It additionally regulates gene expression and apoptosis; is an essential cofactor of uncoupling proteins; and has anti-inflammatory, redox modulatory, and neuroprotective effects." "Administration of CoQ10 improves hyperalgesia and quality of life in patients with fibromyalgia. The evidence base for the effectiveness of treatment with CoQ10 may be explained via its ability to ameliorate oxidative stress and protect mitochondria."

Morse CA, Quan SF, Mays MZ et al. 2004.  Is there a relationship between obstructive sleep apnea and gastroesophageal reflux disease?  Clin Gastroenterol Hepatol. 2(9):761-768.  “Subjective reports of sleep quality were affected by GERD severity, but an objective correlation between OSA and GERD was lacking. This may suggest that GERD and OSA are common entities that share similar risk factors, but appear not to be causally linked.”

Morton DL, Sandhu JS, Jones AK. 2016. Brain imaging of pain: state of the art. J Pain Res. 9:613-624. "Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain's role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained". This article is a good look at how imagery has changed the way we look at pain, and what is possible now. Free Article

Mosca F, Persi A, Stracqualursi A et al. 2004.  [The abdominal wall: an overlooked cause of pain]  G Chir 25(6-7):245-250.  Abdominal wall TrPs are often overlooked causes of pain and other symptoms often misdiagnosed as visceral in origin.  It is strongly suggested that patients be assessed for TrPs.  If they are treated and the TrPs return, perpetuating factors may then be identified and brought under control.  A visceral-TrP loop may be the problem, but identification and prompt treatment of abdominal and other TrPs can often avoid “... inappropriate diagnostic tests, unsatisfactory treatment and high costs.”

Mosca F, Persi A, Stracqualursi A et al. 2004.  [The abdominal wall: an overlooked cause of pain.]  G Chir 25(6-7):245-250.  [Italian]  Pain from abdominal wall trigger points is frequently misdiagnosed.

Mosch B, Verena Hagena V, Herpertz S, et al. Brain morphometric changes in fibromyalgia and the impact of psychometric and clinical factors: a volumetric and diffusion-tensor imaging study. Arthritis Res Ther. 2023 May 19;25(1):81. "Our results suggest a variety of distinct structural brain changes in FM, particularly affecting areas involved in pain and emotion processing such as the thalamus, putamen, and insula." Free article (Germany) [So many studies have show brain changes in FM, but we don't yet know what they mean. DJS]

Moshrif A, Mosallam A, Abu-Zaid MH, et al. Evaluating the effect of delayed diagnosis on disease outcome in fibromyalgia: A multi-center cross-sectional study. J Pain Res. 2023 Apr 22;16:1355-1365. "Early FM diagnosis is associated with lower SSS (symptom severity scale), total severity scale, and FM tender points, indicating a less severe condition."

Motivala SJ, Sollers J, Thayer J et al. 2006.  Tai chi chih acutely decreases sympathetic nervous system activity in older adults.  J Gerontol A Biol Sci Med Sci. 61(11):1177-1180.  “TCC performance led to acute decreases in sympathetic activity, which could not be explained by physical activity alone.”  [As FMS is associated with up-regulation of the sympathetic nervous system, t’ai chi chuan may be helpful for FMS. DJS]

Motley CP, Maxwell ML. 2010. Fibromyalgia: helping your patient while maintaining your sanity. Prim Care. 37(4):743-755. "In caring for the patient with fibromyalgia, the primary care provider benefits from an understanding of fibromyalgia as a distinct entity. Evidence-based diagnostic criteria for fibromyalgia can be used in all individuals who present with multiple site pain, fatigue, and poor sleep. Planning therapy for individuals with fibromyalgia often involves using both pharmacologic and nonpharmacologic treatment in the primary care setting." [The multiple site pain is generally caused by myofascial trigger points. One can't understand and treat FM without understanding the co-existing conditions that often cause it. DJs]

Mountz, J. M. , L. A. Bradley and G. S. Alarcon. 1998. Abnormal functional activity of the central nervous system in fibromyalgia syndrome. Am J Med Sci 315(6):385-396.

Mousavi-Khatir R, Talebian S, Toosizadeh N et al. 2018. Disturbance of neck proprioception and feed-forward motor control following static neck flexion in healthy young adults. J Electromyogr Kinesiol. 41:160-167. This study from Iran indicated that prolonged neck flexion (10 minutes!) can affect proprioception and anticipatory neck motions "... due to mechanical and neuromuscular changes in the viscoelastic cervical spine structures. These changes in sensory-motor control may be a risk factor for neck pain and injury." [TrPs can activate quickly, and that may be what is happening here. DJS]

Mousavi-Khatir SR, Fernandez-de-Las-Penas C, Saadat P, et al. 2021.The effect of adding dry needling to physical therapy in the treatment of cervicogenic headache: A randomized controlled trial. Pain Med. Oct 23; Online ahead of print. "Dry needling has a positive effect on pain and disability reduction, cervical range of motion and deep cervical flexor muscles performance in patients with cervicogenic headache and active trigger points, although the clinical relevance of the results was small."

Mtibaa K, Thomson A, Nichols D et al. 2017. Hyperthermia-induced neural alterations impair proprioception and balance. Med Sci Sports Exerc. [Aug 31 Epub ahead of print] "The current study suggests that hyperthermia impairs the proprioception and balance parameters measured. These observations might be due to heat-induced alterations in efferent and afferent signals to and from the muscle." [This could affect trigger point-impaired patients significantly during hotter times. DJS]

Mu R, Li C, Zhu JX et al. 2013. National survey of knowledge, attitude and practice of fibromyalgia among rheumatologists in China. Int J Rheum Dis. 16(3):258-263. "The awareness and perception of FM are still low among Chinese rheumatologists. Continuing medical education on FM is needed for improving the quality of health care in China." [Much the same could be said of all countries. DJS]

Mucci V, Demori I, Rapallo, et al. Vestibular disability/handicap in fibromyalgia: A questionnaire study. J Clin Med. 2022 Jul 11;11(14): 4017. "Fibromyalgia (FM) is a poorly understood, central pain processing disorder characterized by a broad range of symptoms, such as chronic pain, sleep disruption, chronic fatigue, and psychosomatic symptoms. In addition, recent studies have shown that FM patients also experience dizziness…. We found that FM participants were significantly affected by vestibular symptoms, which correlated with FM-associated pain and non-pain symptoms. The dizziness reported by FM participants showed peculiar features suggesting an FM-intrinsic mechanism of vestibular dysfunction, possibly linked to migraine and dysautonomia conditions. Correlations between dizziness and depressive mood (or neuroticism), revealed an impact of dizziness on psychological status, leading to depressive reactions and interpersonal difficulties, and possibly involving a noxious, self-sustained stress condition. In conclusion, data showed a manifesting dizziness condition in FM patients that warrants careful clinical attention due to its possible inherent role in the syndrome." [It would be interesting to examine these patients for co-existing TrPs that could be causing dizziness and contributing to chronic pain, sleep disruption, chronic fatigue, and those "psychosomatic" symptoms. DJS]

Mueller C, Fang YHD, Jones C, et al. Evidence of neuroinflammation in fibromyalgia syndrome: a [18F]DPA-714 positron emission tomography study. Pain. 2023 Jun 15. Online ahead of print. "Overall, increasing evidence supports the hypothesis that FM involves microglia-mediated neuroinflammation in the brain."

Muir B, Boot B, Hamilton M. Can a structural leg length discrepancy contribute to persistent concussion symptoms? A case report. J Can Chiropr Assoc. 2022 Dec;66(3):300-309. "Ongoing, post-concussion, vestibulo-ocular/cervical-ocular disruption due to an underlying structural leg length discrepancy as a contributing factor has not been previously described in the literature. A case of PCS with initial conservative treatment of their structural leg length discrepancy and subsequent vestibulo-ocular/cervical-ocular rehabilitation is presented."

Mulkoglu C, Ayhan F. 2020. The impact of coexisting fibromyalgia syndrome on disease activity in patients with psoriatic arthritis and rheumatoid arthritis: A cross-sectional study. Mod Rheumatol. Oct 2;1-7. "The patients with concomitant FMS had higher disease activity parameters (DAS28 and BASDAI) than those without FMS".

Muller KG, Richter A, Bieber C et al.  2004.  [no title given].  Z Arztl Fortbild Qualitatssich 98(2):95-100. [German].  “Conditions affecting the musculoskeletal system are the cause of approximately 25% of absenteeism from work...The physician-patient relationship is burdened with resignation and frustration on both sides....The patient’s active involvement in the decision making process is expected to improve the physician-patient relationship.  One aspect of this shared decision- making process is the evaluation and possibly modification of treatment decisions.”

Muller KG, Richter A, Bieber C et al. 2004.  The process of shared decision making in chronic pain patients: Evaluation and modification of treatment decisions.  Z Arztl Fortbild Qualitatssich 98(2):95-100. [German].

Muller-Ehrenberg H, Thorwesten L. 2007.  Frequency and importance of trigger points in the case of sports-related shoulder pain.  J Musculoskel Pain 15 (Supp 13):33 item 55.  [Myopain 2007 Poster]  “Trigger points [TrPs] can often be diagnosed when patients complain about sports-related shoulder pain, and they contribute considerably to the symptoms.  Including the examination for TrP will therefore broaden the understanding of the cause of shoulder pain.”

Muller-Ehrenberg H, Thorwesten L. 2007.  Improvement of sports-related shoulder pain after treatment of trigger points using focused extracorporeal shock wave therapy regarding static and dynamic force development, pain relief and sensomotoric performance.  J Musculoskel Pain 15 (Supp 13):33 item 56.  [Myopain 2007 Poster]  “The treatment of trigger points using focused ESWT (extracorporeal shock wave therapy) significantly improves the pain symptoms as well as the performance of athletes suffering from acute or chronic shoulder pain.”  This study used piezoelectric shock waves, with significant reduction in pain and return to healthier movement.

Mullins C, Bavendam T, Kirkali Z et al. 2015. Novel research approaches for interstitial cystitis/bladder pain syndrome: thinking beyond the bladder. Transl Androl Urol. 4(5):524-533. "… epidemiological studies have revealed that IC/BPS is commonly associated with other chronic pain conditions, including fibromyalgia, irritable bowel syndrome and chronic fatigue syndrome. These observations suggest that IC/BPS may involve systemic pathophysiology, including alterations of the central nervous system in some patients. Furthermore, there may be multiple causes and contributing factors that manifest in the symptoms of IC/BPS leading to multiple patient sub-groups or phenotypes. Innovative research is necessary to allow for a more complete description of the relationship between this syndrome and other disorders with overlapping symptoms." Free PMC Article [Hmmm. Even the NIH is finding that interactive diagnoses might be a better way to deal with chronic conditions. DJS]

Mullins JF, Hoch MC, Nitz AJ. 2020. Novel application of dry needling for neuropathic myofascial ankle pain and dysfunction following insidious integumentary infection: A case report. J Bodyw Mov Ther. 24(2):138-143." A 33-year-old male serving on active duty in the United States Air Force was referred to physical therapy for decreased ankle range of motion and pain, eight weeks after an integumentary infection on his ankle. The infection was complicated by tissue loss requiring skin grafting for closure. Two months of traditional rehabilitation was unsuccessful and this patient was referred for DN treatment…. This case report represents a unique application of DN to an atypical patient presenting with neuropathic myofascial pain syndrome that demonstrated improvement with DN as the sole intervention."

Mullins JF, Nitz AJ, Hoch MC. 2019. Dry needling equilibration theory: A mechanistic explanation for enhancing sensorimotor function in individuals with chronic ankle instability. Physiother Theory Pract. Jul 16:1-10. "Dry needling equilibration theory (DNET) states that proprioception is improved following DN in the lower extremity by changing the muscle's length-tension relationship and leveraging minor acute discomfort to improve muscle spindle afferent information via the gamma motor system. The application of DNET for individuals with CAI may provide a mechanistic explanation for improved descending cortical output, resulting in enhanced sensorimotor function."

Munguia-Izquierdo D, Legaz-Arrese A. 2007. Exercise in warm water decreases pain and improves cognitive function in middle-aged women with fibromyalgia.  Clin Exp Rheumatol. 25(6):823-830.  “An exercise therapy three times per week for 16 weeks in a warm-water pool is an adequate treatment to decrease the pain and severity of FM well as to improve cognitive function in previously unfit women with FM and heightened painful symptomatology.”

Munipalli B, Strothers S, Rivera F, et al. Association of vitamin B12, vitamin D, and thyroid-stimulating hormone with fatigue and neurologic symptoms in patients with fibromyalgia. Mayo Clin Proc Innov Qual Outcomes. 2022 Jul 31;6(4):381-387. "Objective: To assess the association between vitamin B12 (B12) deficiency and the prevalence of fatigue and prespecified neurologic symptoms in patients with fibromyalgia…. This is the first study to report the association of B12 in patients with fibromyalgia complaining of fatigue. This symptom was prevalent in our group of patients with fibromyalgia with B12 deficiency, regardless of whether the cutoff point was 400 or 350 ng/L."

Munoz Ladron de Guevara C, Fernandez-Serrano MJ, Reyes Del Paso GA et al. 2018. Executive function impairments in fibromyalgia syndrome: Relevance of clinical variables and body mass index. PLoS One. 13(4):e0196329. "Several investigations suggest the presence of deterioration of executive function in fibromyalgia syndrome (FMS). The study quantified executive functions in patients with FMS. A wide array of functions was assessed, including updating, shifting and inhibition, as well as decision making and mental planning. Moreover, clinical variables were investigated as possible mediators of executive dysfunction, including pain severity, psychiatric comorbidity, medication and body mass index (BMI).... Among clinical variables, BMI and pain severity explained the largest proportion of performance variance....This study demonstrated impairments in executive functions of updating, shifting inhibition, decision making and planning in FMS. While the mediating role of pain in cognitive impairments in FMS had been previously established, the influence of BMI is a novel finding. Overweight and obesity should be considered by FMS researchers, and in the treatment of the condition."

Mur, E., A. Drexler, J. Gruber, F. Hartig and V. Gunther. 1999. [No title available]. Wien MedWochenschr 149(19-20):561-3 [German].

Muraleetharan D, Fadich A, Stephenson C et al. 2018. Understanding the impact of fibromyalgia on men: Findings from a nationwide survey. Am J Mens Health. [Jan 1:1557988317753242 Epub ahead of print] "Fibromyalgia (FM) is a serious condition that affects approximately four million people in the United States, and is underdiagnosed in men. The objective of this study was to understand this phenomenon by examining multiple impacts of fibromyalgia on men in regard to interactions in society and the U.S. health system. A qualitative survey was administered to 1,163 respondents both online and in-person in Tennessee, Virginia, Maryland, and Washington, DC. Thematic analyses of the survey responses suggest that men with FM have negative experiences with (1) physical and mental health, (2) quality of life, (3) relationships, and (4) careers as a result of FM. Interactions with health-care providers were deterred by (1) potential for misdiagnosis or dismissal of symptoms, (2) stigma of having a condition primarily affecting women, (3) differences in treatment of men and women with FM, and (4) need for health education resources. These findings dictate a need to improve communication between health-care providers and male FM patients."

Murayama RA, Stuginski-Barbosa J, Moraes NP et al. 2009. Toothache referred from auriculotemporal neuralgia: case report. Int Endod J. 42(9):845-851.  This is yet another case report demonstrating that TrPs can cause toothache that does not originate from the tooth, but is instead a referral pain from the TrPs.

Murner, J. 2002.  Brain injury as a result of whiplash injury: a controversy.  J Whiplash and Rel Dis 1(1):77-84.  “Despite disagreements, it is clear from the literature that brain injury can result from whiplash.”

Murphy SL, Phillips K, Williams DA et al. 2012. The role of the central nervous system in osteoarthritis pain and implications for rehabilitation. Curr Rheumatol Rep. [Aug 10 Epub ahead of print]. It has been known for some time that central nervous system (CNS) pain amplification is present in some individuals with osteoarthritis; the implications of this involvement, however, are just starting to be realized....This review article focuses on current literature describing CNS amplification in osteoarthritis by discussing peripheral sensitization, central sensitization, and central augmentation, and the clinical manifestation of central augmentation referred to as centralized pain, and offers considerations for rehabilitation treatment and future directions for research.

Murray B, Yashar BM, Uhlmann WR et al. 2013. Ehlers-Danlos syndrome, hypermobility type: A characterization of the patients' lived experience. Am J Med Genet A. 161(12):2981-2988. "Hypermobility type Ehlers-Danlos syndrome (EDS-HT) is an inherited connective tissue disorder clinically diagnosed by the presence of significant joint hypermobility and associated skin manifestations. This article presents a large-scale study that reports the lived experience of EDS-HT patients, the broad range of symptoms that individuals with EDS-HT experience, and the impact these symptoms have on daily functioning. A 237-item online survey, including validated questions regarding pain and depression, was developed. Four hundred sixty-six (466) adults (90% female, 52% college or higher degree) with a self-reported diagnosis of EDS-HT made in a clinic or hospital were included. The most frequently reported symptoms were joint pain (99%), hypermobility (99%), and limb pain (91%). They also reported a high frequency of other conditions including chronic fatigue (82%), anxiety (73%), depression (69%), and fibromyalgia (42%). Forty-six percent of respondents reported constant pain often described as aching and tiring/exhausting. Despite multiple interventions and therapies, many individuals (53%) indicated that their diagnosis negatively affected their ability to work or attend school. Our results show that individuals with EDS-HT can experience a wide array of symptoms and co-morbid conditions. The degree of constant pain and disability experienced by the majority of EDS-HT respondents is striking and illustrates the impact this disorder has on quality of life as well as the clinical challenges inherent in managing this complex connective tissue disorder."

Muscolino JE. 2013. Abdominal wall triggerpoint case study. J Bodyw Mov Ther 17(2):151-156. "When myofascial pain syndrome is responsible for a patient's condition and is not recognized by the patient's medical advisors, the patient may be put through a plethora of testing procedures to find the cause of the patient's pain, and prescribed medications in an effort to treat the patient's symptoms, The case review presented here involves a patient with severe anterior abdominal pain, with a history of Crohn's disease, who experienced a long and difficult medical process before a diagnosis of myofascial pain syndrome was made."

Mustonen L, Aho T, Harno H et al. 2018. What makes surgical nerve injury painful? A 4-9 year follow-up of patients with intercostobrachial nerve resection in women treated for breast cancer. Pain. [Sep 17 Epub ahead of print] "Nerve injury during breast cancer surgery can cause neuropathic pain (NP). It is not known why some, but not all, patients develop chronic postsurgical neuropathic pain (CPSNP) after the same nerve injury. In the present study, we examined 251 breast cancer survivors with surgeon-verified intercostobrachial nerve (ICBN) resection to identify factors that associate with CPSNP....Preoperative pain in the surgical area, other chronic pains, and breast-conserving surgery associated with future CPSNP. Other chronic pains, increased psychological burden, and insomnia, both before surgery and at the follow-up, associated with CPSNP... Patients with established CPSNP showed increased pain sensitivity in CPT and higher levels of inflammatory markers, suggesting that central sensitization and inflammation may associate with the maintenance of CPSNP." [It would be interesting to know if these CPSNP patients had TrPs. DJS]

Mutlu P, Zateri C, Zohra A et al. 2020. Prevalence of obstructive sleep apnea in female patients with fibromyalgia. Saudi Med J. 41(7):740-745. "Of the participants, 65.9% were found to have obstructive sleep apnea (OSA). Patients with OSA were older and had a higher disease activity score for FM. A strong positive correlation was identified between the apnea-hypopnea index (AHI) and the FA disease activity score. A negative correlation was found between AHI and the subscales of SF-36…. A clinical assessment of female patients with FM requires a multidisciplinary approach, and patients with excessive daytime sleepiness in particular are recommended to undergo polysomnography. The authors believe that the early detection and treatment of accompanying OSA will contribute not only to the quality of life, but also to the survival of patients with FM."

Muzammil S, Cooper HC. 2011. Acute pancreatitis and fibromyalgia: Cytokine link. N Am J Med Sci. 3(4):206-208. [Case Report] "There is a known increase in levels of cytokines in patients with fibromyalgia. Part of the pathophysiology of acute pancreatitis is related to raised cytokines and immune deregulations. We hypothesize that elevated levels of cytokines in fibromyalgia has led to acute pancreatitis in our patient. Further epidemiological research on the incidence of pancreatitis in cytokine mediated conditions such as fibromyalgia is required."

Myburgh C, Kildsgaard K, Damsgaard T, et al. 2021.Consistency of dry-needling interventions across high-quality randomized trials: A critical systematic exploration of intervention reporting and fidelity J Manipulative Physiol Ther. Sep;44(7):546-557."Across the RCTs (randomized clinical trials) included in this review, substantial heterogeneity in the choice and reporting of DN was evident….. The development and adoption of standardized intervention guidelines is recommended to enhance uniform and nuanced reporting of DN interventions."

Myburgh C, Lauridsen HH, Hartvigsen J. 2010. Standardized manual palpation of myofascial trigger points in relation to neck/shoulder pain; the influence of clinical experience on inter-examiner reproducibility. Man Ther. [Aug 31 Epub ahead of print]. "Identification of clinically relevant TrPs of the upper trapezius musculature is reproducible when performed by two experienced clinicians...." [This study conforms what has been found before. Myofascial TrP diagnosis by palpation is repeatable with trained, experienced care providers. It takes a concerted effort to get that experience. DJS]

Myers T. 2014. Spatial medicine -- A call to 'arms'. J Bodyw Mov Ther. 18:94-98. "A comprehensive and coherent approach to spatial patterning in human posture and movement is visible on the horizon. Advances in the study of fascia, neural plasticity, and epigenetics allow an overarching theory to unite all who work in human movement from osteopaths to personal trainers. Trainers, rehab specialists, manual therapists and physical educators are joining to embrace and develop this unifying construct to help our growing children meet the demands of the 21st century electronic environment."

Myers T. 2007. Treatment approaches for three shoulder “tethers.”   J Bodywork Movement Ther 1(11):3-8.  This excellent article offers an in depth look at three common “sticking points” in the shoulder complex (subclavious, pectoralis minor, and teres minor) and how to treat them.

Na SUKT, Lee YM, Park JH et al. 2020. Low vitamin D levels in post-menopausal women are associated with complex regional pain syndrome type I in surgically treated distal radius fractures. J Orthop Surg Res. Aug 14;15(1):328. "Background: Complex regional pain syndrome type I (CRPS I) is a chronic devastating condition and a relatively common complication of distal radius fractures (DRF). The purpose of this study was to investigate the relationship of vitamin D levels in surgically treated post-menopausal women with CRPS I occurrence in DRF…. Conclusion: Lower vitamin D levels in post-menopausal women can increase CRPS I occurrence in distal radius fractures." Free article. [Korea]

Nabekura T, Morishima S, Cover T.L. et al. 2003.  Recovery from lactacidosis-induced glial cell swelling with aid of exogenous anion channels.  Glia 41(3):247-59. Cerebral edema associated with lactacidosis or head trauma may be associated with swelling in astrocytes, and may be treated by introducing anion channel activity. [This may be relevant to some of the cerebral swelling and cognitive dysfunction noted in fibromyalgia. DJS]

Nacir B, Genc H, Duyur Cakit B et al. 2012. Evaluation of Upper Extremity Nerve Conduction Velocities and the Relationship between Fibromyalgia and Carpal Tunnel Syndrome. Arch Med Res. [Jul 24 Epub ahead of print]. "We determined an increased rate of CTS (carpal tunnel syndrome) and decreased NCV (nerve conduction velocities) in the upper extremities in patients with FS. We should consider that complaints of paresthesia and pain in hands, increasing especially at night, observed in FS may mask that CTS can be an associated illness."

Nadeau SE. 2015. Opioids for chronic noncancer pain: To prescribe or not to prescribe-What is the question? Neurology. [Jul 2 Epub ahead of print.] "The recent American Academy of Neurology position paper by Franklin, 'Opioids for chronic noncancer pain,' suggests that the benefits of opioid treatment are very likely to be substantially outweighed by the risks and recommends avoidance of doses above 80-120 mg/day morphine equivalent. However, close reading of the primary literature supports a different conclusion: opioids have been shown in randomized controlled trials (RCTs) to be highly effective in the treatment of chronic nonmalignant pain; long-term follow-up studies have shown that this effectiveness can be maintained; and effectiveness has been limited in many clinical trials by failure to take into account high variability in dose requirements, failure to adequately treat depression, and use of suboptimal outcome measures. Frequency of side effects in many RCTs has been inflated by overly rapid dose titration and failure to appreciate the high interindividual variability in side effect profiles. The recent marked increase in incidence of opioid overdose is of grave concern, but there is good reason to believe that it has been somewhat exaggerated. Potential causes of overdose include inadequately treated depression; inadequately treated pain, particularly when compounded by hopelessness; inadvertent overdose; concurrent use of alcohol; and insufficient practitioner expertise. Effective treatment of pain can enable large numbers of patients to lead productive lives and improve quality of life. Effective alleviation of suffering associated with pain falls squarely within the physician's professional obligation. Existing scientific studies provide the basis for many improvements in pain management that can increase effectiveness and reduce risk."

Nadler SF, Feinberg JH, Reisman S, Stitik TP, DePrince ML, Hengehold D, Weingand K. 2001.  Effect of topical heat on electromyographic power density spectrum in subjects with myofascial pain and normal controls: a pilot study. Am J Phys Med Rehabil Nov;80(11):809-15.  Myofascial pain patients responded differently to exercise and heat challenge.  This may indicate a difference in muscle physiology.

Nagpal AS, Moody EL. 2017. Interventional management for pelvic pain. Phys Med Rehabil Clin N Am. 28(3):621-646. "Interventional procedures can be applied for diagnostic evaluation and treatment of the patient with pelvic pain, often once more conservative measures have failed to provide relief. This article reviews interventional management strategies for pelvic pain. We review superior and inferior hypogastric plexus blocks, ganglion impar blocks, transversus abdominis plane blocks, ilioinguinal, iliohypogastric and genitofemoral blocks, pudendal nerve blocks, and selective nerve root blocks. Additionally, we discuss trigger point injections, sacroiliac joint injections, and neuromodulation approaches."

Nahin RL, Boineau R, Khalsa PS et al. 2016. Evidence-based evaluation of complementary health approaches for pain management in the United States. Mayo Clin Proc. 91(9):1292-1306. "Although most pain is acute and resolves within a few days or weeks, millions of Americans have persistent or recurring pain that may become chronic and debilitating. Medications may provide only partial relief from this chronic pain and can be associated with unwanted effects. As a result, many individuals turn to complementary health approaches as part of their pain management strategy. This article examines the clinical trial evidence for the efficacy and safety of several specific approaches-acupuncture, manipulation, massage therapy, relaxation techniques including meditation, selected natural product supplements (chondroitin, glucosamine, methylsulfonylmethane, S-adenosylmethionine), tai chi, and yoga-as used to manage chronic pain and related disability associated with back pain, fibromyalgia, osteoarthritis, neck pain, and severe headaches or migraines".

Naja ZM, Al-Tannir MA, Zeidan A et al. 2007.  Nerve stimulator-guided repetitive paravertebral block for thoracic myofascial pain syndrome.  Pain Pract. 7(4):348-351.  [This treatment may be useful for chronic MTPs resistant to standard treatments]

Nakagawa T, Kaneko S. 2010. Spinal Astrocytes as Therapeutic Targets for Pathological Pain. J Pharmacol Sci. [Nov 11 Epub ahead of print]. "Development of next-generation analgesics requires a better understanding of the molecular and cellular mechanisms underlying pathological pain. Accumulating evidence suggests that the activation of glia contributes to the central sensitization of pain signaling in the spinal cord. The role of microglia in pathological pain has been well documented, while that of astrocytes still remains unclear. After peripheral nerve inflammation or injury, spinal microglia are initially activated and subsequently sustained activation of astrocytes is precipitated, which are implicated in the induction and maintenance of pathological pain. Astrocytic activation is caused by the production of diffusible factors from primary afferent neurons (neuron-to-astrocyte signals) and activated microglia (microglia-to-astrocyte signals). Although astrocyte-to-neuron signals implicated in pathological pain is poorly understood, activated astrocytes, as well as microglia, produce proinflammatory cytokines and chemokines, which lead to adaptation of the dorsal horn neurons. Furthermore, it has been suggested that glial glutamate transporters in the spinal astrocytes are down-regulated in pathological pain and that up-regulation or functional enhancement of these transporters prevents pathological pain. This review will briefly discuss novel findings on the role of spinal astrocytes in pathological pain and their potential as a therapeutic target for novel analgesics."

Nakai Y, Oe K, Matsuno R, et al. Effect of self-myofascial release of the lower back on myofascial gliding, lumbar flexibility, and abdominal trunk muscle strength: A crossover study. Sports (Basel). 2023 Aug 2;11(8):147. "Roller massage has been recognized as an effective intervention for managing various conditions…. This study aimed to examine the effect of the self-myofascial release of the lower back on myofascial gliding, lumbar flexibility, and abdominal trunk muscle strength using a roller massager…. The self-myofascial release of the lower back using a roller massager improved the lumbar/fascia gliding, lumbar flexibility, and abdominal trunk muscle strength compared to static stretching."

Nakajima F, Aratani S, Fujita H et al. 2016. A case of fibromyalgia involving pain throughout the body treated with site-specific targeted pain control. Springerplus. 5(1):1027. "We report the case of a patient who developed fibromyalgia after left femoral neck fracture. After several caudal epidural blocks for lumbar pain, the pain throughout the body and abnormal discomfort in the laryngopharyngeal region reduced. Site-specific targeted pain control was effective in treating his pain and discomfort…. The present case suggests that treatment targeting symptoms in one part of the body might produce a systemic therapeutic effect in patients with fibromyalgia." Free PMC Article [Controlling the pain sources can control the central sensitization of FM. DJS]

Nam TS, Choi SY, Park DJ et al. 2014. The Overlap between Fibromyalgia Syndrome and Myotonia Congenita. J Clin Neurol. [Nov 11 Epub ahead of print.] "Fibromyalgia syndrome (FMS) is a complex disorder characterized by chronic widespread pain (CWP), multiple areas of tenderness, sleep disturbance, fatigue, and mood or cognitive dysfunction. Myotonia congenita (MC) is an inherited myopathic disorder that is caused by mutations in the gene encoding the skeletal muscle chloride channel, which can infrequently manifest as generalized muscle cramps or myalgia….The first case was a 33-year-old woman who complained of CWP and chronic headache occurring during pregnancy, and the second case was a 37-year-old man with CWP and depression who suffered from cold-induced muscle cramps. These two patients were initially diagnosed with FMS by rheumatologists, based on CWP of longer than 3 months duration and mechanical tenderness in specific body regions. However, these two FMS patients were subsequently also diagnosed with MC….These two cases are the first report of an overlap of CWP between FMS and MC." Free Article [This study from Korea highlights two cases of this co-morbidity. I have seen one, and that person also had myofascial trigger points. I suspect that congenital frequently has these co-morbidities, as do most chronic conditions. DJS]

Nantz E, Liu-Seifert H, Skijarevski V. 2009.  Predictors of premature discontinuation of treatment in multiple disease states.  Patient Prefer Adherence. 3:31-43.  "Contrary to the conventional belief that premature treatment discontinuation is primarily related to adverse events, our findings suggest lack of therapeutic response also plays a significant role in patient attrition.  This research highlights the importance of systematic monitoring of therapeutic response in clinical practice as a measure to prevent patients’ discontinuation from pharmacological treatments."

Napadow V, Edwards RR, Cahalan CM et al. 2012. Evoked Pain Analgesia in Chronic Pelvic Pain Patients Using Respiratory-Gated Auricular Vagal Afferent Nerve Stimulation. Pain Med. [May 8 Epub ahead of print]. "Objective: Previous vagus nerve stimulation (VNS) studies have demonstrated antinociceptive effects, and recent noninvasive approaches, termed transcutaneous-vagus nerve stimulation (t-VNS), have utilized stimulation of the auricular branch of the vagus nerve in the ear. The dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration can optimize t-VNS.. RAVANS (respiratory-gated auricular vagal afferent nerve stimulation) produced promising antinociceptive effects (in CPP patients) for quantitative sensory testing (QST) outcomes reflective of the noted hyperalgesia and central sensitization in this patient population."

Napadow V, Harris RE. 2014. What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of 'centralized' pain? Arthritis Res Ther. 16(5):425. "Research suggests that fibromyalgia is a central, widespread pain syndrome supported by a generalized disturbance in central nervous system pain processing…. In recent years, brain neuroimaging techniques have heralded a revolution in our understanding of chronic pain, as they have allowed researchers to non-invasively (or minimally invasively) evaluate human patients suffering from various pain disorders. This review will outline recent applications of the complementary imaging techniques - fcMRI and 1H-MRS - to improve our understanding of fibromyalgia pathophysiology and how pharmacological and non-pharmacological therapies contribute to analgesia in these patients. A better understanding of the brain in chronic pain, with specific linkage as to which neural processes relate to spontaneous pain perception and hyperalgesia, will greatly improve our ability to develop novel therapeutics. Neuroimaging will play a growing role in the translational research approaches needed to make this a reality."

Naschitz JE, Rozenbaum M, Fields MC et al. 2005.  Cardiovascular reactivity in fibromyalgia: evidence for pathogenic heterogeneity.  J Rheumatol. 32(2):335-339.  “Patients with FM represent a heterogenous group with respect to their pattern of cardiovascular reactivity.”

Naschitz JE, Rosner I, Rozenbaum M et al. 2003.  The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome.  QJM 96(2):133-142.  The particular dysautonomia in CFS is different from that occurring in fibromyalgia and other illnesses, and this difference can be measured with objective testing.

Nasirzadeh Y, Ahmed S, Monteiro S et al. 2017. A survey of healthcare practitioners on myofascial pain criteria. Pain Pract. [Nov 1 Epub ahead of print] "The goal of this study was to assess agreement on signs and symptoms of myofascial pain for chiropractors, physicians, and registered massage therapists….Descriptive statistics, including mean response values, were used to assess which signs or symptoms were most often associated with myofascial pain….There was poor agreement within chiropractors, physicians, and registered massage therapists on the criteria that represent MPS. Physicians and massage therapists were in agreement on four and disagreed on two items. Chiropractors were in agreement on a different set of signs and symptoms relative to physicians and registered massage therapists, and they expressed neutrality on most statements in the questionnaire. Registered massage therapists were in most agreement amongst each other as a group… relative to chiropractors…and physicians….Our results suggest that there is a lack of agreement within and between health care practitioner groups on the signs and symptoms that define myofascial pain syndrome. We suggest the demonstrated variability in diagnostic knowledge be remedied through the establishment and universal use of official validated criteria. Future research should focus on developing criteria specific to myofascial pain syndrome. Finally, knowledge translation strategies may be implemented to increase clinician knowledge of available criteria."

Nassar Y, Richter S. 2019. Gastroparesis in non-diabetics: Associated conditions and possible risk factors. Gastroenterology Res. 11(5):340-345. "Gastroparesis is a syndrome characterized by delayed gastric emptying in the absence of any mechanical cause. While often associated with diabetes mellitus, most cases of gastroparesis are idiopathic. The purpose of the present paper is to review the co-morbid conditions that most likely associate with non-diabetic gastroparesis.... Notable conditions that were found to be most closely linked with gastroparesis were: chronic pancreatitis, end stage renal disease, irritable bowel syndrome, systemic lupus erythematosus, fibromyalgia, and venous thromboembolism. Some of the implications of these findings are briefly discussed."

Natelson BH. 2013. Brain dysfunction as one cause of CFS symptoms including difficulty with attention and concentration. Front Physiol. 4:109. "We have been able to reduce substantially patient pool heterogeneity by identifying phenotypic markers that allow the researcher to stratify chronic fatigue syndrome (CFS) patients into subgroups. To date, we have shown that stratifying based on the presence or absence of comorbid psychiatric diagnosis leads to a group with evidence of neurological dysfunction across a number of spheres. We have also found that stratifying based on the presence or absence of comorbid fibromyalgia leads to information that would not have been found on analyzing the entire, unstratified patient group. Objective evidence of orthostatic intolerance (OI) may be another important variable for stratification and may define a group with episodic cerebral hypoxia leading to symptoms. We hope that this review will encourage other researchers to collect data on discrete phenotypes in CFS to allow this work to continue more broadly. Finding subgroups of CFS suggests different underlying pathophysiological processes responsible for the symptoms seen. Understanding those processes is the first step toward developing discrete treatments for each."

Navarro RP. 2009. Contemporary management strategies for fibromyalgia. Am J Manag Care. 15(7 Suppl):S197-218.  “A roundtable meeting that comprised clinical, patient advocacy, and managed care experts discussed issues regarding the diagnosis and management of fibromyalgia.  The panel agreed that earlier diagnosis and treatment, additional education for the medical community, and appropriate management by health plans, including patient access to US Food and Drug Administration-approved fibromyalgia medications, are needed.  In addition, physicians, payers, and patient advocates must work to improve clinical, economic, and quality-of-life outcomes for fibromyalgia patients.  Finally, treatment and diagnostic guidelines must be updated as advances in disease management are made (including approvals of three new pharmacologic agents), and development of a therapeutic category for “fibromyalgia” on payer formularies is needed.”  [This is a fine paper, and it must be done for myofascial pain as well, as these two diagnoses often occur in the same patients. DJS]

Navarro-Santana MJ, Valera-Calero JA, Romanos-Castillo G, et al. 2022. Immediate effects of dry needling on central pain processing and skin conductance in patients with chronic nonspecific neck pain: A randomized controlled trial. J Clin Med. 2022 Nov 8;11(22):6616. "Our results suggested that dry needling applied to patients with chronic nonspecific neck pain produced an immediate decrease in mechanical hyperalgesia at local sites and produced an increase in skin conductance as compared with sham needling. No changes in central pain processing were observed. A single session of sham or real dry needling was similarly effective for decreasing related disability, pain intensity, catastrophism, and kinesiophobia levels."

Nebel MB, Gracely RH. 2009. Neuroimaging of fibromyalgia.  Rheum Dis Clin North Am. 35(2):313-327.  “Using a wide array of techniques, these studies have found differences in opioid receptor binding, in the concentration of metabolites associated with neural processing in pain-related regions, in functional brain networks, and in regional brain volume and white matter tracks.  A common theme of all of these methods is that they provide information that may be pertinent to the otherwise unobservable and poorly treated symptoms of persistent widespread chronic pain.”  [There may be many ways in which pain is uncontrolled in FM.  FM is real, even though there are no easy and widely available tests for it.  It is to be hoped that those doctors and other professionals who “don’t believe in FM,” as if it were on par with a horoscope, will read good studies such as this and become educated.  FM is not a faith-based belief, it is medical and scientific fact. DJS]

Neblett R, Cohen H, Choi Y et al. 2013. The Central Sensitization Inventory (CSI): Establishing Clinically-Significant Values for Identifying Central Sensitivity Syndromes in an Outpatient Chronic Pain Sample. J Pain. [Mar 9 Epub ahead of print]. "Central sensitization (CS) is a proposed physiological phenomenon in which central nervous system neurons become hyperexcitable, resulting in hypersensitivity to both noxious and non-noxious stimuli. The term central sensitivity syndrome (CSS) describes a group of medically indistinct (or nonspecific) disorders, such as fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome, for which CS may be a common etiology. In a previous study, the central sensitization inventory (CSI) was introduced as a screening instrument for clinicians to help identify patients with a CSS…. The CSI is a new self-report screening instrument to help identify patients with CSSs, including fibromyalgia. The present study investigated CSI scores in a heterogeneous pain population, with a large percentage of CSSs, and a normative nonclinical sample to determine a clinically relevant cutoff value."

Neblett R, Hartzell MM, Mayer TG et al. 2016. Establishing clinically relevant severity levels for the Central Sensitization Inventory. Pain Pract. [Mar 15 Epub ahead of print.] "The aim of this study was to create and validate severity levels for the central sensitization inventory (CSI), a valid and reliable patient-reported outcome instrument designed to identify patients whose presenting symptoms may be related to a central sensitivity syndrome (CSS; eg, fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome), with a proposed common etiology of central sensitization (CS)…. Compared to the non-CSS patient subsample, the score distribution of the CSS patient subsample was skewed toward the higher severity ranges. CSI mean scores moved into higher severity levels as the number of individual CSS diagnoses increased. Patients who scored in the extreme CSI severity level were more likely to report previous diagnoses of fibromyalgia, chronic fatigue syndrome, temporomandibular joint disorder, tension/migraine headaches, and anxiety or panic attacks…. CSI severity levels were also associated with patient-reported depressive symptoms, perceived disability, sleep disturbance, and pain intensity…." [This study from the World Institute of Pain alerts us to the existence of the Central Sensitization Inventory as well as validates it. Care Providers should become aware of this tool to monitor central sensitization. DJS]

Nedergaard M. 2013. Neuroscience. Garbage truck of the grain. Science 340 (6140):1529-1530. [This article focuses predominantly on neurodegenerative diseases, but the effect of the proposed glial cell network in clearing excess interstitial fluid from the brain is, I believe, very relevant to patients with fibromyalgia. During or after the process of neurodegeneration, abnormal proteins can be difficult to process and remove from the brain. This is the case in Alzheimer's disease, wherein tau and beta-amyloid can accumulate. Cytosolic proteins may be released into the brain's interstitial space, indicating that there may be a pathway for extracellular disposal of these neurotoxic wastes. (This may also be a possibility for quinolinic acid, which can be produced instead of serotonin in the tryptophan kynurenine alternative metabolic pathway found in some fibromyalgia patients.) There are aquaporin 4 (AQP4) channels on the vascular endfeet of astrocytes, a type of glial cell, that facilitate the flow from around the outsides of the arteries to the interstitial space. The cerebrospinal fluid exchanges with the interstitial fluid, driving waste products from the arteries to the veins. The interstitial fluid flows around the veins to the lymphatic system in the neck area, and the material in the interstitial fluid eventually finds its way into the lymph system. Up to 80% of the large proteins and soluble wastes and metabolic by-products in the brain are removed by this system of glial cells and lymph vessels working through the interstitial space. Dr. Nedergaard calls this system in the brain the "glymphatic system". When AQP4 is dysfunctional or inappropriately located, as can occur after trauma or stroke (or perhaps exposure to quinolinic acid if the kynurenine metabolic pathway is in use) this can result in excess proteins, solutes and perhaps fluid accumulation. Perhaps defects in the glymphatic system could be part of the cause of fibrofog and cerebral fluid accumulation in fibromyalgia patients. Excess interstitial fluid in the body has been observed in some fibromyalgia and insulin-resistant patients. It is extremely difficult to rid the interstitial space of accumulated fluid. The research being done by Dr. Nedergaard and others may offer insight and hope to some of us who have diffuse interstitial swelling and confusional states. DJS]

Neeck G. 2004.  Pain and the neuroendocrine system.  J Musculoskeletal Pain 12(3/4):45.  This brief summary explains the relation of the HPA-axis activation and the stress system to acute and chronic pain.

Neeck, G. and W. Riedel. 1999 Hormonal perturbations in fibromyalgia syndrome. Ann NY Acad Sci 22:876:325-38.

Negrini, S. 2000. Operation overload: kids’ backpacks. Science News 157(2):31.

Negrini, S., R. Carabalona and P. Sibilla. 1999. Backpack as a daily load for children. Lancet354 (9194):1974.

Nehls V. 2018. [Osteoarthropathies and myopathies associated with disorders of the thyroid endocrine system]. Dtsch Med Wochenschr. 143(16):1174-1180. [Article in German] "Triiodothyronine (T3) is a key regulator of bone, muscle and articular cartilage. Musculoskeletal symptoms of hyperthyroidism include loss of bone mass finally leading to osteoporosis and weakness of the skeletal musculature. Hypothyroidism on the other side frequently leads to muscle stiffness and cramping and, occasionally, results in rhabdomyolysis. To prevent terminal differentiation of chondrocytes with consecutive cartilage degeneration, cartilage probably depends on exact regulation of local T3 availability by the intracellular deiodinase system. Recent findings underline the importance of local T3 generation by deiodinase type 2 and support the existence of local hypo- or hyperthyroidism.In the review, the implications of the recent literature for current understanding of osteoarthritis, myopathies and diabetic osteoarthropathy will be discussed. Further emphasis will be placed on the association of autoimmune thyroiditis with musculoskeletal diseases and fibromyalgia." [Thyroid disorders, including thyroid resistance, tend to be common coexisting conditions in chronic myofascial pain and dysfunction and fibromyalgia. DJS]

Nelson, D. V. and D. M. Novy. 1996. Psychological characteristics of reflex sympathetic dystrophy versus myofascial pain syndromes. Reg Anesth 21(3):202-208.

Nelson LS, Hoffman RS. 1998.  Intrathecal injection: unusual complication of trigger-point injection therapy.  Ann Emerg Med. 32(4):506-508.  “Trigger-point injection therapy is a common procedure in primary care medicine and emergency medicine and is generally considered safe.  A 28-year-old woman experienced respiratory depression and hemiplegia after the injection of a superficial trapezius trigger point.  The patient required emergency tracheal intubation for ventilatory support.  Computed tomography of her head revealed pneumocephalus.  She recovered fully over the course of 24 hours.  Intrathecal injection during a trigger-point injection is a previously unreported complication of trigger-point injection therapy.”

Nelson S, Cunningham N, Peugh J et al. 2017. Clinical profiles of young adults with juvenile-onset fibromyalgia with and without a history of trauma. Arthritis Care Res (Hoboken). [Jan 13 Epub ahead of print.] "The current study is the first controlled study to examine the differential outcomes between JFM participants with and without a history of trauma. Two group comparisons between JFM participants and healthy controls were consistent with previous research. Further, our findings indicate that JFM participants with a trauma history experience greater psychological but not physical impairment than JFM participants without a trauma history."

Neto HP, Bicalho E, Bortolazzo G. 2021. Interoception and emotion: A potential mechanism for intervention with manual treatment. Cureus. Jun 25;13(6):e15923. "Interoception is considered a perception pathway as important as the exteroceptive pathways for determining responses to maintain homeostasis. There is evidence about the influence of the interoception on emotional responses as these expressions are considered to be a combination of physical, environmental and individual beliefs. A large percentage of afferent fibers in the body are related to free nerve endings which, when stimulated, reach the insular cortex that participates in the process of emotions. The viscera afferent fibers represent 5% to 15% of all these inputs. Evidence emerges that demonstrates the importance of visceral health as part of the treatment of patients with emotional imbalances. It can be postulated that manual treatment applied to visceral fasciae can assist in interoceptive balance and have a positive impact on emotions. Therefore, the objective of the present study is to discuss the concepts of interoception, central sensitization, emotional health and visceral manual treatment."

Neubauer, D. N. 1999. Sleep problems in the elderly. Am Fam Physician 59(9):2551-8, 2559-60.

Neumann DJ. 2014. July 2014 book reviews. Orthop Sports Phys Ther. 44(7):542-546. JOSPT offers invited reviews of current titles. The July 2014 column includes 6 reviews of the following books: Physical Therapy Management of Patients With Spinal Pain: An Evidence-Based Approach; Traumatology for the Physical Therapist; Evidence-Based Rehabilitation: A Guide to Practice, Third Edition; Healing Through Trigger Point Therapy: A Guide to Fibromyalgia, Myofascial Pain, and Dysfunction; Your Headache Isn't All in Your Head: Neuroscience Education for Patients With Headache Pain; and Disorders of the Shoulder: Diagnosis and Management Package, Third Edition.

Neumeister MW, Neumeister EL. 2020. Fibromyalgia. Clin Plast Surg. Apr;47(2):203-213. "Surgery may not be the most appropriate management of some of these pain conditions like fibromyalgia. It may even be more difficult to discern some surgical conditions from points of heightened sensitivity in the fibromyalgia patient. Close attention to the current and past medical history in such patients should aid the surgeon in his attempt to rid the patient of painful conditions through surgery."

Neville CE, Carrubba AR, Li Z, et al. 2021. Association of coccygodynia with pelvic floor symptoms in women with pelvic pain. PM R. Sep 17. Online ahead of print. "Sixty three (49.6%) of 127 women with pelvic pain presented with coccygodynia and 64…did not. Women with coccygodynia had significantly higher rates of muscle spasm… higher visual analog scale (VAS) pain scores… higher rates of outlet dysfunction constipation… and higher rates of fibromyalgia…. On pelvic exam, women with coccygodynia were significantly more likely to have sacrococcygeal joint hypomobility… coccygeus muscle spasm… anococcygeal ligament pain… external anal sphincter pain/spasm… and impaired pelvic floor muscle (PFM) coordination… This study demonstrates a strong link between coccygodynia, pelvic floor symptoms, and pelvic pain, and highlights the importance of screening for and identifying coccyx pain when evaluating women with pelvic pain."

Neville CE, Fitzgerald CM, Mallinson T et al. 2012. A preliminary report of musculoskeletal dysfunction in female chronic pelvic pain: a blind study of examination findings. J Bodyw Mov Ther. 16(1):50-56. "Abdominal findings on musculoskeletal exam are more common in women with self-reported CPP. Women with CPP might benefit from a faster time to diagnose and improved treatment outcomes if a musculoskeletal contribution to CPP was identified earlier."

Newcomb LW, Koltyn KF, Morgan WP et al. 2010. The Influence of Preferred versus Prescribed Exercise on Pain in Fibromyalgia. Med Sci Sports Exerc. [Nov 11 Epub ahead of print]. "It is concluded that the women with FM who participated in this study experienced significant improvements in pain following exercise. The results from this study are novel and indicate that recommendations for exercise prescription for individuals with FM should consider the preferred intensity exercise model as a strategy to reduce pain."

Ng S.Y. 1999. Hair calcium and magnesium levels in patients with fibromyalgia: a case center study. J Manipulative Physiol Ther 22(9):586-93. Calcium and magnesium supplements may be indicated as an adjunctive treatment of fibromyalgia.

Nguyen BM. 2013. Myofascial trigger point falls in the elderly, idiopathic knee pain and osteoarthritis: An alternative concept. Med Hypotheses. [April 5 Epub ahead of print]. "Knee alignment and associated pathological abnormal forces transmitted through the knee is thought to provoke joint protective mechanism in reflex arthrogenic muscle inhibition (AMI) and the start of the idiopathic knee osteoarthritic process. The current prevailing hypothesis is AMI initiates quadriceps muscle weakness, cause aberrant loading of the knee joint and focal cartilage destruction. This paper investigates for evidence in the literature if this conceptual framework is consistent with the clinical evidence, and if there is an alternative explanation to AMI hypothesis for the pathogenesis of idiopathic knee osteoarthritis. One crucial question yet to be answered by the AMI hypothesis is; where are the initial aggravating factors of reflex AMI emanate from? AMI hypothesis relies on joint damage and changes in joint homeostasis to provoke a reflex arthrogenous response which can be found late in the development of knee OA. Myofascial trigger point (MTrP) hypothesis only relies on muscle tightness, pain and weakness to detect early pathological neuromuscular changes including knee instability and falls in the elderly. AMI is implicated in the knee OA pathological process but much later on when there are changes in joint homeostasis and joint cartilage damage have occurred. Falls in the elderly are a result of early pathological neuromuscular changes. The MTrP hypothesis is more sensitive and advanced in the early detection of neuromuscular impairment and pathological changes, allowing early intervention, prevention of falls in the elderly and idiopathic knee osteoarthritis." [Researchers are discovering that bones follow muscles, and that it is the muscle contracture by TrPs causing the wear and tear on bony areas of joints that leads to osteoarthritis. DJS]

Nguyen BM. 2010. Trigger point therapy and plantar heel pain: A case report. Foot (Edinb). [Oct 26 Epub ahead of print]. Myofascial trigger points are a common cause of the condition often called plantar fasciitis. Trigger point therapy for plantar fasciitis has been neglected in medicine. [We can not afford to describe a set of symptoms and call that a diagnosis. We must look at the cause and treat the cause. DJS]

Nguyen MH, Kruse A. 2012. A randomized controlled trial of Tai chi for balance, sleep quality and cognitive performance in elderly Vietnamese. Clin Interv Aging. 7:185-90. "Tai chi is beneficial to improve balance, sleep quality, and cognitive performance of the elderly."

Nguyen RH, Ecklund AM, Maclehose RF et al. 2012. Co-morbid pain conditions and feelings of invalidation and isolation among women with vulvodynia. Psychol Health Med. [Feb 13 Epub ahead of print]. "Having a co-morbid condition with vulvodynia, as well as having an increasing number of co-morbid conditions with vulvodynia, was significantly associated with the presence of feeling both invalidated and isolated. Chronic fatigue syndrome was the co-morbidity most strongly associated with feelings invalidation and isolation. One or more co-morbid pain conditions in addition to vulvodynia were significantly associated with psychosocial wellbeing.... future studies should explore the utility of promoting validation of women's pain conditions and reducing social isolation for women with chronic pain. [It is most unfortunate that the co-existing condition most interactive with and often causative of vulvodynia, chronic myofascial pain, was not considered among these conditions. DJS]

Nguyen RH, Veasley C, Smolenski D. 2013. Latent class analysis of comorbidity patterns among women with generalized and localized vulvodynia: preliminary findings. J Pain Res. 6:303-309. "The pattern and extent of clustering of comorbid pain conditions with vulvodynia is largely unknown. However, elucidating such patterns may improve our understanding of the underlying mechanisms involved in these common causes of chronic pain….This novel work provides insight into potential shared mechanisms of vulvodynia by describing that a prominent comorbidity pattern involves having both irritable bowel syndrome and fibromyalgia. In addition, the prevalence of a multiple comorbidity class pattern increases with increasing severity of vulvar pain." [Until the medical world understands that many symptoms often labeled generalized and localized vulvodynia or fibromyalgia are actually due to or sustained by myofascial trigger points, and that those TrPs are the critical generating co-existing condition, researchers are going to miss the critical (trigger) point. DJS]

Nicassio PM, Schuman CC. 2005.  The prediction of fatigue in fibromyalgia.  J Musculoskeletal Pain 13(1).  “The data demonstrated that passive coping contributed to a dysfunctional cycle characterized by heightened pain and depressive symptomatology, leading to greater fatigue.  The continued effort to develop effective interventions to reduce maladaptive coping efforts in FMS is warranted by these findings.”

Nicassio P.M., Moxham E.G., Schuman C.E. et al. 2002.  The contribution of pain, reported sleep quality, and depressive symptoms to fatigue in fibromyalgia.  Pain 100(3):271-9. The study indicates that the fatigue of fibromyalgia is due to poor sleep quality. Lack of restorative sleep is a perpetuating factor that must be addressed to alleviate patient’s fatigue.

Nichols TW Jr, Gaiteri C. 2014. Morton's foot and pyridoxal 5'-phosphate deficiency: Genetically linked traits. Med Hypotheses. 83(6):644-648. Vitamin B6 is an essential vitamin needed for many chemical reactions in the human body. It exists as several vitamins forms but pyridoxal 5'-phosphate (PLP) is the phosphorylated form needed for transamination, deamination, and decarboxylation. PLP is important in the production of neurotransmitters, acts as a Schiff base and is essential in the metabolism of homocysteine, a toxic amino acid involved in cardiovascular disease, stroke, thrombotic and Alzheimer's disease. This report announces the connection between a deficit of PLP with a genetically linked physical foot form known as the Morton's foot. Morton's foot has been associated with fibromyalgia/myofascial pain syndrome. Another gene mutation methylenetetrahydrofolate reductase (MTHFr) is now being recognized much commonly than previous with chronic fatigue, chronic Lyme diseases and as "the missing link" in other chronic diseases. PLP deficiency also plays a role in impaired glucose tolerance and may play a much bigger role in the obesity, diabetes, fatty liver and metabolic syndrome. Without the Schiff-base of PLP acting as an electron sink, storing electrons and dispensing them in the mitochondria, free radical damage occurs! The recognition that a phenotypical expression (Morton's foot) of a gene resulting in deficiency of an important cofactor enzyme pyridoxal 5'-phosphate will hopefully alert physicians and nutritionists to these phenomena. Supplementation with PLP, L5-MTHF, B12 and trimethylglycine should be used in those patients with hyperhomocysteinemia and/or MTHFR gene mutation.

Nicol AL, Sieberg CB, Clauw DJ et al. 2016. The association between a history of lifetime traumatic events and pain severity, physical function, and affective distress in patients with chronic pain. J Pain. [Sep 15 Epub ahead of print.] "Evidence suggests that pain patients who report lifetime abuse experience greater psychological distress, have more severe pain and other physical symptoms, and greater functional disability. The aim of the present study was to determine the associations between a history of lifetime abuse and affective distress, fibromyalgia-ness (as measured by the 2011 Fibromyalgia Survey), pain severity and interference, and physical functioning. A cross-sectional analysis of 3,081 individuals presenting with chronic pain was performed using validated measures and a history of abuse was assessed via patient self-report… individuals with a history of abuse… had greater depression, greater anxiety, worse physical functioning, greater pain severity, worse pain interference, higher catastrophizing, and higher scores on the fibromyalgia survey criteria….. Mediation models showed that both the fibromyalgia survey score and affective distress independently mediate the relationship between abuse and pain severity and physical functioning…. This article examines the associations between a history of lifetime abuse and affective distress, fibromyalgia-ness, pain severity and interference, and physical functioning in chronic pain patients".

Nicol AL, Wu II, Ferrante FM. 2014. Botulinum toxin type A injections for cervical and shoulder girdle myofascial pain using an enriched protocol design. Anesth Analg. 118(6):1326-1335. BoNT-A injected directly into painful muscle groups improves average pain scores and certain aspects of quality of life in patients experiencing severe cervical and shoulder girdle myofascial pain.

Nicola M, Correia H, Ditchburn G, Drummond PD. The Pain-Invalidation Scale: measuring patient perceptions of invalidation toward chronic pain. J Pain. Published online July 14, 2022. "Increasing evidence reveals the damaging impact of having one's chronic pain symptoms invalidated through disbelief, discrediting, and critical judgement. In other instances, a caregiver's over-attentiveness to the daily tasks of individuals with pain can be problematic, potentially undermining rehabilitation. The aim of this study was to develop an instrument to measure different aspects of invalidation perceived by people with chronic pain… The Pain-IS demonstrates sound psychometric properties and may serve as a valuable tool for use by clinicians in the detection of pain-invalidation issues, as a first step in patient pain management….Links between pain-invalidation and pain levels, as well as functional detriment, highlight the importance of having one's chronic pain experience heard, believed, and accepted. The Pain-Invalidation Scale is designed to identify domains where invalidation of the patient's pain should be addressed to promote emotional processing, treatment adherence, and improved outcomes."

Nicola M, Correia H, Ditchburn G, et al. Invalidation of chronic pain: a thematic analysis of pain narratives. Disabil Rehabil. 2021 Mar;43(6):861-869. "Many people with chronic pain report feeling disbelieved or disparaged by others regarding their pain symptoms. Given the widely documented relationship between stress and pain, the importance of identifying psychosocial stressors such as pain-invalidation is apparent. This study was designed to identify and illustrate using first-person narratives, the effects of pain-invalidation by the self, family, friends, and healthcare professionals, toward individuals with chronic pain…. Five major pain-invalidation themes were revealed: Not being believed, lack of compassion, lack of pain awareness/ understanding, feeling stigmatized, and critical self-judgement. Themes additional to pain-invalidation included: Threats to Self-Image, Loss of Identity, and Isolation…. Themes were largely interrelated and, together, build a picture of how levels of perceived social unacceptability of pain symptoms can impact on the emotional state and self-image of those with chronic pain. As such, pain-invalidation may potentially impede help-seeking or the effectiveness of therapeutic interventions…. Pain-invalidation can arise through a lack of understanding by others in the social network about having chronic pain. Pain-invalidation may be a barrier to seeking therapy for pain management and rehabilitation, and thus, efforts to identify and acknowledge invalidation experiences may be beneficial in the rehabilitation process."

Nicolaidis C. 2011. Police Officer, Deal-Maker, or Health Care Provider? Moving to a Patient-Centered Framework for Chronic Opioid Management. Pain Med. [May 3 Epub ahead of print]. "How we frame our thoughts about chronic opioid therapy greatly influences our ability to practice patient-centered care. Even providers who strive to be nonjudgmental may approach clinical decision-making about opioids by considering if the pain is real or they can trust the patient. Not only does this framework potentially lead to poor or unshared decision-making, it likely adds to provider and patient discomfort by placing the provider in the position of a police officer or a judge. Similarly, providers often find themselves making deals with patients using a positional bargaining approach. Even if a compromise is reached, this framework can potentially inadvertently weaken the therapeutic relationship by encouraging the idea that the patient and provider have opposing goals. Reframing the issue can allow the provider to be in a more therapeutic role. As recommended in the American Pain Society/American Academy of Pain Medicine guidelines, providers should decide whether the benefits of opioid therapy are likely to outweigh the harms for a specific patient (or sometimes, for society) at a specific time. This article discusses how providers can use a benefit-to-harm framework to make and communicate decisions about the initiation, continuation, and discontinuation of opioids for managing chronic nonmalignant pain. Such an approach focuses decisions and discussions on judging the treatment, not the patient. It allows the provider and the patient to ally together and make shared decisions regarding a common goal. Moving to a risk-benefit framework may allow providers to provide more patient-centered care, while also increasing provider and patient comfort with adequately monitoring for harm."

Niddam DM, Chan RC, Lee SH et al. 2007.  Central modulation of pain evoked from myofascial trigger point.  Clin J Pain. 23(5):440-448.  “Low-intensity low-frequency electrostimulation delivered within a myofascial trigger point (MTP) has been used as intervention to deactivate MTPs.”  “The applied intervention most likely involves supraspinal pain control mechanisms related to both antinociception and regulation of pain affect.”

Niddam DM, Chan Rc, Lee SH et al. 2008.  Central representation of hyperalgesia from myofascial trigger point.  NeuroImage. 39:1299-1306.  Using functional MRI, imaging regions that are dysfunctional in FM patients, researchers used a needle electrode or pressure to stimulate MTPs.  Both stimulations produced a higher pain response than normal controls, with “significantly enhanced somatosensory activity (SI, SII, inferior pareital, mid insula) and limbic (anterior insula) activity and suppressed right dorsal hippocampal activity in patients compared with controls.”  The results show that the hyperalgesic state in MTP patients is associated with abnormal brain activity in the areas that process stimulus activity and negative affect.  [This study indicates that MTPs may contribute significantly to central sensitization. DJS]

Niddam DM, Lee SH, Su YT et al. 2016. Brain structural changes in patients with chronic myofascial pain. Eur J Pain. [Jun 28 Epub ahead of print.] "Myofascial trigger points (MTrPs) are a highly prevalent source of musculoskeletal pain. Prolonged ongoing nociceptive (pain) input from MTrPs may lead to maladaptive changes in the central nervous system. However, it remains unknown whether pain from MTrPs is associated with brain atrophy. In addition, stress, which may contribute to the formation of MTrPs, is also known to affect brain structures. Here, we address whether structural brain changes occur in patients with chronic pain originating from MTrPs and whether such changes are related to pain or stress… Patients exhibited normal stress levels but lowered pain thresholds. GM (grey matter) atrophy was found in dorsal and ventral prefrontal regions in patients. The GM density of the right dorsolateral prefrontal cortex correlated with pain thresholds in patients, i.e., the more atrophy, the lower pain threshold. GM atrophy was also found in the anterior hippocampus, but the atrophy was neither related to pain nor stress…. It remains unclear whether the observed atrophy contributes to the development of the chronic pain state or is caused by the ongoing nociceptive input…. Chronic myofascial pain, caused by myofascial trigger points, is associated with localized brain atrophy in areas involved in pain processing and modulation, among others. These findings extend previous knowledge about peripheral and spinal changes to the supraspinal level." [Cognitive deficits are often due to more than fibromyalgia. We can treat the contributors of cognitive pain that are treatable, and see what we have left. DJS]

Nielsen LA, Henriksson KG. 2007.  Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia): the role of central and peripheral sensitization and pain disinhibition.  Best Pract Res Clin Rheumatol. 21(3):465-480.  “In FMS there is strong scientific support for the statement that the biological part of the syndrome is a longstanding or permanent change in the function of the nociceptive nervous system that can be equated with a disease.”  “FMS may be the far end of a continuum that starts with chronic localized/regional musculoskeletal pain and ends with widespread chronic disabling pain.”

Nielsen SS, Skou ST, Larsen AE et al. The effect of occupational engagement on lifestyle in adults living with chronic pain: A systematic review and meta-analysis. Occup Ther Int. 2022 Jun 13;2022:7082159. "This study is aimed at investigating the effect of including occupational engagement in chronic pain interventions on lifestyle… Including occupational engagement in chronic pain interventions may increase short-term physical activity and long-term sleep quality. Due to the few available RCTs including occupational engagement in chronic pain treatment for adults living with chronic pain, further high-quality RCTs are needed and will likely change the conclusion."

Nielson WR, Merskey H.2001.  Psychosocial aspects of fibromyalgia. Curr Pain Headache Rep 5(4):330-7. The opinion that fibromyalgia syndrome (FMS) is a psychiatric disorder or can be caused by stress or abuse is unproven and can be of potential harm to patients. Care providers should be aware of "possible undue influences on medical opinion by agencies providing health care and research funding".

Nigam G, Riaz M, Hershner SD,et al. 2015. Sleep related scratching: A distinct parasomnia? J Clin Sleep Med. Aug 12. [Epub ahead of print] "Pruritus (itching) during the sleep period can present as a symptom of dermatological or systemic disease, or as a parasomnia. Sleep related scratching as a primary parasomnia [sleep associated dysfucnion], exclusively confined to sleep in the absence of coexisting dermatological disorders, has not been well described. This case series describes three such patients, and discusses potentially relevant pathophysiology that can underlie itching or pain. Such cases of sleep related scratching may merit nosologic classification apart from previously defined parasomnias."

Nijs J, Daenen L, Cras P et al. 2011. Nociception Affects Motor Output: A Review on Sensory-motor Interaction with Focus on Clinical Implications. Clin J Pain. [Jun 27 Epub ahead of print]. "Nociception-induced motor inhibition might prevent effective motor retraining. In addition, the sympathetic nervous system responds to chronic nociception with enhanced sympathetic activation. Not only motor and sympathetic output pathways are affected by nociceptive input, afferent pathways (proprioception, somatosensory processing) are influenced by tonic muscle nociception as well.... The clinical consequence of the shift in thinking is to stop trying to restore normal motor control in case of chronic nociception. Activation of central nociceptive inhibitory mechanisms, by decreasing nociceptive input, might address nociception-motor interactions."

Nijs J, Kosek E, Van Oosterwijck J et al. 2012. Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exercise or not to exercise? Pain Physician. 15(3 Suppl):ES205-213. "Exercise is an effective treatment for various chronic pain disorders, including fibromyalgia, chronic neck pain, osteoarthritis, rheumatoid arthritis, and chronic low back pain. Although the clinical benefits of exercise therapy in these populations are well established (i.e., evidence based), it is currently unclear whether exercise has positive effects on the processes involved in chronic pain (e.g., central pain modulation). A dysfunctional response of patients with chronic pain and aberrations in central pain modulation to exercise has been shown, indicating that exercise therapy should be individually tailored with emphasis on prevention of symptom flares. The paper discusses the translation of these findings to rehabilitation practice together with future research avenues."

Nijs J, Loggia ML, Polli A et al. 2017. Sleep disturbances and severe stress as glial activators: key targets for treating central sensitization in chronic pain patients? Expert Opin Ther Targets. 21(8):817-826. This review indicates that glial cell overactivation in animals can cause central nervous system sensitization and chronic pain states. "Aberrant glial activity in chronic pain might have been triggered by severe stress exposure, and/or sleeping disturbances, each of which are established initiating factors for chronic pain development…. Potential treatment avenues include several pharmacological options for diminishing glial activity, as well as conservative interventions like sleep management, stress management and exercise therapy. Pharmacological options include propentofylline, minocycline, beta-adrenergic receptor antagonists, and cannabidiol. Before translating these findings from basic science to clinical settings, more human studies exploring the outlined mechanisms in chronic pain patients are needed."

Nijs J, Malfliet A, Ickmans K et al. 2014. Treatment of central sensitization in patients with 'unexplained' chronic pain: an update. Expert Opin Pharmacother. 15:1-13. "Central sensitization (CS) is present in a variety of chronic pain disorders, including whiplash, temporomandibular disorders, low back pain, osteoarthritis, fibromyalgia, headache, lateral epicondylalgia among others. In spite of our increased understanding of the mechanisms involved in CS pain, its treatment remains a challenging issue. Areas covered: An overview of the treatment options we have for desensitizing the CNS in patients with CS pain is provided. These include strategies for eliminating peripheral sources of nociception, as well as pharmacotherapy and conservative interventions that primarily address top-down (i.e., brain-orchestrated) mechanisms. Expert opinion: A combination of different strategies, each targeting a different 'desensitizing' mechanism, might prove superior over monotherapies. Such combined therapy may include both bottom-up and top-down (e.g., opioids, combined ?-opioid receptor agonist and noradrenaline reuptake inhibitor drugs) strategies. Topically applied analgesic therapies have strong potential for (temporally) decreasing peripheral nociceptive input (bottom-up approach). Targeting metabolic (e.g., ketogenic diets) and neurotrophic factors (e.g., decreasing brain-derived neurotrophic factor) are promising new avenues for diminishing hyperexcitability of the CNS in central sensitization pain patients. Addressing conservative treatments, pain neuroscience education, cognitive behavioral therapy and exercise therapy are promising treatments for CS pain."

Nijs J, Torres-Cueco R, van Wilgen CP et al. 2014. Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain. Pain Physician. 17(5):447-457. "It is proposed that the classification of central sensitization pain entails 2 major steps: the exclusion of neuropathic pain and the differential classification of nociceptive versus central sensitization pain. For the former, the International Association for the Study of Pain diagnostic criteria are available for diagnosing or excluding neuropathic pain. For the latter, clinicians are advised to screen their patients for 3 major classification criteria, and use them to complete the classification algorithm for each individual patient with chronic pain. The first and obligatory criterion entails disproportionate pain, implying that the severity of pain and related reported or perceived disability are disproportionate to the nature and extent of injury or pathology (i.e., tissue damage or structural impairments). The 2 remaining criteria are 1) the presence of diffuse pain distribution, allodynia, and hyperalgesia; and 2) hypersensitivity of senses unrelated to the musculoskeletal system (defined as a score of at least 40 on the Central Sensitization Inventory….Clinicians can use the proposed classification algorithm for differentiating neuropathic, nociceptive, and central sensitization pain." Free Article

Nijs J, Van Houdenhove B, Oostendorp RA. 2009.  Recognition of central sensitization in patients with musculoskeletal pain: application of pain neurophysiology in manual therapy practice.  Man Ther. [Dec 23 Epub ahead of print] "The diagnosis/assessment of central sensitization in individual patients with musculoskeletal pain is not straightforward; however, manual therapists can use information obtained from the medical diagnosis, combined with the medical history of the patient, as well as the clinical examination and the analysis of the treatment response in order to recognize central sensitization.  The clinical examination used to recognize central sensitization entails the distinction between primary and secondary hyperalgesia."

Nimmerjahn A, Kirchhoff F, Helmchen F. 2005.  Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.  Science 308(5726):1314-1318.  “Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases.  By using in vivo two-photo imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions.  Blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patrolling to shielding of the injured site."  [Microglia are highly active, monitoring and directing much of the general health of the brain.]

Niraj G, Richards CJ. 2020. Leiomyosarcoma of the small intestine presenting as abdominal myofascial pain syndrome (AMPS): case report. Scand J Pain. 2020 Sep 24. Online ahead of print. "A female patient presenting with chronic abdominal pain was initially diagnosed as abdominal myofascial pain syndrome. The report details the possible facilitation of the diagnosis of a rare, highly aggressive small bowel tumour by interventional treatment for abdominal myofascial pain syndrome". [TrPs are the great mimic, and we must remember those conditions that they mimic. Zebras and giraffes exist, and we cannot allow them to trample patients. DJS]

Nishioka K, Uchida T, Usui C et al. 2016. High prevalence of anti-TSH receptor antibody in fibromyalgia syndrome. Int J Rheum Dis. [Nov 30 Epub ahead of print.] "For determining thyroid function in 207 FMS patients, we tested for the titers of free tri-iodothyronine, free thyroxine, thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) and anti-TSH receptor antibody (TRAb)" The clinical profiles of each group of patients were identical, but there was a high incidence of anti-TSH antibodies in patients with clinical fibromyalgia, especially TRAb.

Nisihara R, Marques AP, Mei A et al. 2016. Celiac disease and fibromyalgia: Is there an association? Rev Esp Enferm Dig. 108(2):107-108. "It has been found that celiac disease (CD) and non-celiac gluten sensitivity (NCGS) have a high prevalence in fibromyalgia (FM) patients. NCGS is a relatively new entity characterized by gastrointestinal and extra-intestinal manifestations in the absence of CD or wheat allergy. It is different from CD because anti-transglutaminase (anti-tTG) or endomysial antibodies (IgA-EmA) are lacking and the intestinal mucosa is normal or with mild abnormalities as increased intraepithelial lymphocytes in the absence of villous atrophy." Free Article

Nitecka-Buchta A, Nowak-Wachol A, Wachol K et al. Myorelaxant effect of transdermal cannabidiol application in patients with TMD: A randomized, double-blind trial. J Clin Med. 2019 Nov 6;8(11). This parallel and double-blind trial in Poland had 60 subjects with TMD divided randomly into a placebo group (average age 23.2 years) and CBD group (average age 22.6 years), topically applied by patients twice a day on the masseter muscle for a period of 14 days. The surface EMG and VAS scale was used. Muscle activity and pain were reduced by the CBD formulation.

Nora DB, Becker J, Elhers JA et al. 2004.  Clinical features of 1039 patients with neurophysiological diagnosis of carpal tunnel syndrome.  Clin Neurol Neurosurg 107(1):64-69.

Nordahi HM, Stiles TC. 2007.  Personality styles in patients with fibromyalgia, major depression and healthy controls.  Ann Gen Psychiatry 6:9.  “These findings suggest that a depressotypic personality style is related to depressive disorder, but not to FMS.”

Nourmoussavi M, Bodmer-Roy S, Mui J et al. 2014. Bladder Base Tenderness in the Etiology of Deep Dyspareunia. J Sex Med. [Sep 21 Epub ahead of print.] "Bladder base tenderness is present in one-third of women with pelvic pain, and contributes specifically to the symptom of deep dyspareunia. Bladder base tenderness was also associated with the presence of an abdominal wall trigger point and with pelvic floor tenderness, suggesting a myofascial etiology and/or nervous system sensitization."

Nunez-Cortes R, Cruz-Montecinos C, Vasquez-Rosel A, et al. 2017. Dry Needling Combined With Physical Therapy in Patients With Chronic Postsurgical Pain Following Total Knee Arthroplasty: A Case Series. J Orthop Sports Phys Ther. 47(3):209-216. "After dry needling combined with therapeutic exercises, patients who had chronic pain following TKA showed clinically significant improvements in pain, range of motion, function, and myofascial trigger points. Future randomized clinical trials should further investigate the effectiveness of this protocol under similar conditions."

Nur Yucel F, Hande Gezer H, Janbubi Jandaulyet J, et al. Clinical and functional impact of central sensitization on patients with familial Mediterranean fever: a cross-sectional study. Turk J Phys Med Rehabil. 2022 Mar 1;68(1):84-90. "Concomitant pain sensitization appears to be related to FMF patients' clinical and functional characteristics. These results suggest taking into consideration CS in the management of FMF patients".

Nye BL, Thadani VM. 2015. Migraine and epilepsy: review of the literature. Headache. 55(3):359-380. "Migraine and epilepsy are disorders that are common, paroxysmal, and chronic. In many ways they are clearly different diseases, yet there are some pathophysiological overlaps, and overlaps in clinical symptomatology, particularly with regard to visual and other sensory disturbances, pain, and alterations of consciousness. Epidemiological studies have revealed that the two diseases are comorbid in a number of individuals….In epilepsy, neuronal overactivity leads to the recruitment of larger populations of neurons firing in a rhythmic manner that constitutes an epileptic seizure. Migraine aura and headaches may act as a trigger for epileptic seizures. Epilepsy is not infrequently accompanied by preictal, ictal, and postictal headaches that often have migrainous features. Genetic links are also apparent between the two disorders, and are particularly evident in the familial hemiplegic migraine syndromes where different mutations can produce either migraine, epilepsy, or both. Also, various medications are found to be effective for both migraine and epilepsy, again pointing to a commonality and overlap between the two disorders."

Oaklander AL, Herzog ZD, Downs H et al. 2013. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. [Jun 5 Epub ahead of print.] "Fibromyalgia is a common, disabling syndrome that includes chronic widespread pain plus other diverse symptoms….In contrast, small-fiber polyneuropathy (SFPN), despite causing similar symptoms, is definitely a disease caused by dysfunction and degeneration of peripheral small-fiber neurons….41% of skin biopsies from fibromyalgia subjects vs. 3% of biopsies from control subjects were diagnostic for SFPN, and MNSI (Michigan Neuropathy Screening Instrument) and UENS (Utah Early Neuropathy Scale) scores were higher among fibromyalgia than control subjects…. Abnormal AFT (Autonomic Function Testing) was equally prevalent suggesting that fibromyalgia-associated SFPN is primarily somatic. Blood tests from all 13 fibromyalgia subjects with SFPN-diagnostic skin biopsies provided insights into etiologies. All glucose tolerance tests were normal, but eight subjects had dysimmune markers, 2 had hepatitis C serologies, and one family had apparent genetic causality. These findings suggest that some patients with chronic pain labeled as "fibromyalgia" have unrecognized small-fiber polyneuropathy, a distinct disease that can be objectively tested for an sometimes definitively treated."

Oaklander AL, Nolano M. Scientific Advances in and Clinical Approaches to Small-Fiber Polyneuropathy: A Review. JAMA Neurol. 2019 Sep 9 [Epub ahead of print] "Small-fiber polyneuropathy involves preferential damage to the thinly myelinated A-delta fibers, unmyelinated C sensory fibers, or autonomic or trophic fibers. Although this condition is common, most patients still remain undiagnosed and untreated because of lagging medical and public awareness of research advances. Chronic bilateral neuropathic pain, fatigue, and nausea are cardinal symptoms that can cause disability and dependence, including pain medication dependence….Initially, patients with idiopathic small-fiber disorders should be screened by medical history and blood tests for potentially treatable causes, which are identifiable in one-third to one-half of patients. Then, secondary genetic testing is particularly important for familial and childhood cases. especially of blood vessels, contributes to diverse symptoms, including postexertional malaise, postural orthostatic tachycardia, and functional gastrointestinal distress. …. Because small fibers normally grow throughout life, improving contributory conditions may permit regrowth, slow progression, and prevent permanent damage. The prognosis is often hopeful for improving quality of life and sometimes for abatement or resolution, particularly in the young and otherwise healthy individuals. Examples include diabetic, infectious, toxic, genetic, and inflammatory causes."

Oberklaid F, Amos D, Liu C et al. 1997.  “Growing pains”: clinical and behavioral correlates in a community sample.  J Dev Behav Pediatr 18(2):102-106.  Parents consider children with growing pains to have different behavioral and temperamental profiles than healthy children.  [There is no acknowledgement in this study that the presence of chronic pain could contribute to the behavior problems, rather than the reverse. DJS]

O’Brien EM, Staud RM, Hassinger AD et al. 2009.  Patient-centered perspective on treatment outcomes in chronic pain.  Pain Med. [Sep 1 Epub ahead of print].  “Results highlight the importance of assessing the patient’s view of successful outcome.  Both fibromyalgia and back pain patients appear to have stringent criteria for success that existing treatments are often unlikely to meet.  Comparison across groups indicated fibromyalgia patients have higher than usual levels of pain, fatigue, distress, and interference.  Interestingly, fibromyalgia patients also require greater changes across domains in order to consider treatment successful, despite rating higher levels of pain, fatigue, distress, and interference as successful.  Recognizing patients’ success criteria and treatment expectations encourages discussion and development of individualized treatment goals, and wider implementation of individualized treatment for chronic-pain populations is encouraged.”

O'Brien EM, Waxenberg LB, Atchison JW et al. 2011. Intraindividual Variability in Daily Sleep and Pain Ratings among Chronic Pain Patients: Bidirectional Association and the Role of Negative Mood. Clin J Pain. [Mar 16 Epub ahead of print]. "These findings suggest that addressing sleep is important in the treatment of individuals with chronic pain."

Oda K, Kim K, Kokubo R et al. 2018. [Chronic Low Back Pain Associated with Gluteus Medius Muscle: A Case Report]. No Shinkei Geka. 46(4):319-323. [Article in Japanese] "We report a case of long-term BuP that was successfully treated with gluteus medius muscle (GMeM) decompression under local anesthesia. A 71-year-old man was referred to our hospital because of long-term BuP and claudication. Left BuP that radiated to the left thigh was observed. The pain was mostly triggered by palpation at the middle of the iliac crest and greater trochanter. Lumbar and pelvic radiograms showed no significant lesions. Lumbar magnetic resonance imaging revealed a mild lumbar spinal canal stenosis at the L4/L5 segment. Based on the evidence of a trigger point and pain relieved after GMeM block injection, we made a diagnosis of GMeM pain. Although several GMeM block injections relieved his pain, the analgesic effect was transient and the claudication remained. Then, we decided to perform GMeM decompression. We made a 5-cm-long skin incision across the trigger point on the buttock. After confirming a wide exposure of the gluteal aponeurosis over the GMeM, we cut and opened it for sufficient GMeM decompression, and the GMeM expansion was confirmed. After surgery, his symptoms immediately improved. No evidence of recurrence was observed 6 months after his treatment. For the treatment of LBP and BuP, GMeM pain would be considered a causative factor. We report that it can be treated with a less invasive surgical technique, which would contribute to good clinical outcome." [Treat the patient, not the imaging. DJS]

Offenbaecher M, Dezutter J, Kohls N et al. 2016. Struggling with adversities of life: The role of forgiveness in patients suffering from fibromyalgia. Clin J Pain. [Aug 31 Epub ahead of print]…. Forgiveness of self and others is beneficially associated with pain, health, quality of life, and anger in FMS patients at levels that are of similar size and direction as in healthy controls. However, FMS patients manifest lower levels of forgiveness of self and others. Therapeutic promotion of forgiveness as a psychosocial coping strategy may help patients with FMS to better manage psychological and physical symptoms, thereby enhancing well-being.

Offenbacher M, Stucki G. 2000. Physical therapy in the treatment of fibromyalgia. Scand J Rheumatol 113: 78-85. "Trigger point injection may reduce pain originating in concomitant trigger points in selected fibromyalgia patients. Massage may reduce muscle tension and may be prescribed as an adjunct with other therapeutic interventions. Acupuncture may reduce pain and increase pain threshold. Biofeedback may positively influence subjective and objective disease measures. TENS may reduce localized musculoskeletal pain in fibromyalgia. … Accordingly. a multidisciplinary approach combining these therapies in a well balanced program may be the most promising strategy and is currently recommended in the treatment of fibromyalgia."

Offenbaecher M, Kohls N, Toussaint LL et al. 2013. Spiritual needs in patients suffering from fibromyalgia. Evid Based Complement Alternat Med. [Nov 20 Epub ahead of print.] "Using a set of standardized questionnaires (i.e., Spiritual Needs Questionnaire, Fibromyalgia Impact Questionnaire, SF-36's Quality of Life, Brief Multidimensional Life Satisfaction Scale, etc.), we enrolled 141 patients (95% women, mean age 58 ± 10 years). Here, needs for inner peace and giving/generativity scored the highest, while existential needs and religious needs scored lowest. Particularly inner peace needs and existential needs correlated with different domains of reduced mental health, particularly with anxiety, the intention to escape from illness, and psychosocial restrictions. Thirty-eight percent of the patients stated needs to be forgiven and nearly half to forgive someone from their past life. Therefore, the specific spiritual needs of patients with chronic diseases should be addressed in clinical care in order to identify potential therapeutic avenues to support and stabilize their psychoemotional situation."

Ofluoglu D, Gunduz OH, Kul-Panza E et al. 2005.  Hypermobility in women with fibromyalgia syndrome.  Clin Rheumatol. [Oct 16 Epub ahead of print]  “Hypermobility syndrome is more common in women with FS than in those in the control group.  Therefore, the relationship between hypermobility and FS should be taken into consideration in the diagnosis and follow-up of women, especially those with widespread pain.”

Oh S, Kim HK, Kwak J et al. 2013. Causes of hand tingling in visual display terminal workers. Ann Rehabil Med. 37(2):221-228. "To offer the basic data about the causes and distribution of hand tingling, symptoms and physical findings, and pressure pain threshold in desk workers… Five physiatrists participated in the screening test composed of history and physical examination. A total of 876 desk workers were evaluated and of them 37 subjects with hand tingling were selected. For further analyzing, detailed history taking and meticulous physical examination were taken. Pressure pain threshold (PPT) at the infraspinatus, upper trapezius, flexor carpi radialis, rhomboideus, and flexor pollicis longus were examined. PPT measurements were repeated three times with two minute intervals by a pressure algometer. Electrodiagnostic study was done to detect potential neurologic abnormalities….THE CAUSES OF HAND TINGLING IN ORDER OF FREQUENCY WERE: myofascial pain syndrome, 68%; cervical radiculopathy, 27%; rotator cuff syndrome, 11%; tenosynovitis, 8%; and carpal tunnel syndrome, 5%. The location of trigger points in the myofascial pain syndrome, which were proven to evoke a tingling sensation to the hand in order of frequency were: infraspinatus, 65.4%; upper trapezius, 57.7%; flexor carpi radialis, 38.5%; rhomboideus 15.4%; and flexor pollicis longus 11.5%. The PPT of the affected side was significantly lower than that of the unaffected side in myofascial pain syndrome (p<0.05)…The most common cause of hand tingling in desk workers was myofascial pain syndrome rather than carpal tunnel syndrome. Common trigger points to evoke hand tingling were in the infraspinatus and upper trapezius."

Oh S, Kim M, Lee M et al. 2017. Effect of myofascial trigger point therapy with an inflatable ball in elderlies with chronic nonspecific low back pain. J Back Musculoskelet Rehabil. [Aug 4 Epub ahead of print] "Myofascial trigger point therapy with an inflatable ball relieved pain and improved physical function in the elderly with CNSLBP (chronic nonspecific low back pain)".

Oh TH, Hoskin TL, Luedtke CA et al. 2012. Predictors of clinical outcome in fibromyalgia after a brief interdisciplinary fibromyalgia treatment program: single center experience. PM R. 4(4):257-263. "Patients with younger age, more years of education (with college or graduate degree), higher baseline FIQ depression score, lower tender point count, and absent abuse history experience greater benefit from a brief fibromyalgia treatment program." [The Mayo Clinic has such a program, and generated this research. It is not known if patients are taught about co-existing myofascial trigger points at this clinic. DJS]

Ohara N, Katada S, Yamada T et al. 2016. Fibromyalgia in a patient with Cushing's Disease accompanied by central hypothyroidism. Intern Med. 55(21):3185-3190. "A 39-year-old woman with a 3-year history of a rounded face developed widespread myalgia. Detailed examinations revealed no disorders that could explain the pain other than concomitant Cushing's disease and central hypothyroidism. Both the hypercortisolemia and hypothyroidism completely resolved after the patient underwent surgery to treat Cushing's disease, but she continued to experience unresolved myalgia and met the diagnostic criteria for fibromyalgia. Few studies have so far investigated patients with fibromyalgia associated with Cushing's syndrome. In our case, the hypothyroidism caused by Cushing's disease probably played an important role in triggering and exacerbating fibromyalgia. This highlights the need to examine the endocrine function in patients with muscle pain." Free Article

Ohayon MM. 2005.  Prevalence and correlates of nonrestorative sleep complaints.  Arch Intern Med. 165(1):35-41.  “Nonrestorative sleep is a frequent symptom in the general population, but its prevalence largely varies between countries.  Nonrestorative sleep affected more frequently the active classes of the population and caused greater daytime impairment than difficulty initiating or maintaining sleep.”

Ohgidani M, Kato TA, Hosoi M et al. 2017. Fibromyalgia and microglial TNF-alpha: Translational research using human blood induced microglia-like cells. Sci Rep. 7(1):11882. "These findings suggest that microglia in patients with fibromyalgia are hypersensitive to ATP. TNF-alpha from microglia may be a key factor underlying the complex pathology of fibromyalgia." Free Article

Ohmori A, Iranami H, Fujii K et al. 2013. Myofascial involvement of supra- and infraspinatus muscles contributes to ipsilateral shoulder pain after muscle-sparing thoracotomy and video-assisted thoracic surgery. J Cardiothorac Vasc Anesth. 27(6):1310-1314. "This study examined the hypothesis that ipsilateral upper extremity elevation for muscle-sparing thoracotomy procedures contributes to the postoperative shoulder pain….These results supported the hypothesis that myofascial involvement contributed, to some extent, to shoulder pain after muscle-sparing thoracotomy with ipsilateral upper extremity elevation."

Okan S, Caglıyan Turk A, Sıvgın H et al. Association of ferritin levels with depression, anxiety, sleep quality, and physical functioning in patients with fibromyalgia syndrome: a cross-sectional study. Croat Med J. 2019 Dec 31;60(6):515-520."Patients with fibromyalgia syndrome have a rather high prevalence of non-anemic iron deficiency. No associations were found between serum ferritin level and anxiety, depression, sleep quality, and physical functioning." [Note: ferritin is the form of iron needed by muscle tissue, and lack of ferritin is a perpetuating factor for trigger points. DJS]

Okhravi SM, Zavveyeh MK, Kalantari KK et al. 2015. A study on the effects of general fatigue on head and neck proprioception in healthy young adults. Ortop Traumatol Rehabil. 17(1):1-6. "Fatigue is one of the factors causing disturbance in proprioception which can be manifested in two ways: general and local. Due to the important role of cervical proprioception on body stability and posture, research on the effects of general fatigue on proprioception helps to better understand its mechanism and to improve the strategies to prevent injury. Therefore, the aim of this study was to identify the effects of general fatigue on head and neck proprioception in young healthy adults….Conclusions: 1. General fatigue increased the repositioning angular error of head and neck. 2. Neck proprioception decreased due to general fatigue. 3. General fatigue increased the risk of neck injury." [This makes sense, as fatigue is a major initiating/aggravating/perpetuating factor of trigger points. DJS]

Okifuji A, Donaldson GW, Barck L et al. 2010. Relationship between fibromyalgia and obesity in pain, function, mood, and sleep. J Pain. [Jun 8 Epub ahead of print]. "Fibromyalgia syndrome (FMS) is a prevalent and disabling chronic pain disorder.… A total of 215 FMS patients completed a set of self-report inventories to assess FMS-related symptoms and underwent the tender point (TP) examination, physical performance testing, and 7-day home sleep assessment. Forty-seven percent of our sample was obese and an additional 30% was overweight. Obesity was related significantly to greater pain sensitivity to TP palpation particularly in the lower body areas, reduced physical strength and lower-body flexibility, shorter sleep duration, and greater restlessness during sleep….The results suggest that obesity may aggregate FMS and weight management may need to be incorporated into treatments."

Okifuji A, Hare BD. 2015. The association between chronic pain and obesity. J Pain Res. 8:399-408. "Obesity and pain present serious public health concerns in our society. Evidence strongly suggests that comorbid obesity is common in chronic pain conditions, and pain complaints are common in obese individuals. In this paper, we review the association between obesity and pain in the general population as well as chronic pain patients." Free PMC Article

Okifuji, A., D. C. Turk and J. J. Sherman. 2000. Evaluation of the relationship between depression and fibromyalgia syndrome: what aren’t all patients depressed?  J Rheumatol 27(1):212-9.

Okumus M, Ceceli E, Tuncay F et al. 2010. The relationship between serum trace elements, vitamin B12, folic acid and clinical parameters in patients with myofascial pain syndrome. J Back Musculoskel Rehabil. 23(4):187-191. "Serum levels of zinc...were significantly decreased in patients with MPS. VAS, total myalgic and BDI scores of patients were significantly higher than the control group....Association between TMS and magnesium, vitamin B12 levels was found statistically significant. BDI (Beck Depression Inventory) score correlated significantly with the serum zinc level...and VAS (Visual Analogue Scale) in patients with MPS....According to the results of this study, it was asserted that trace elements, vitamins may play an important role in the pathophysiology of MPS and psychological factors may also have additional effect."

Oldfield M, MacEachen E, Kirsh B et al. 2015. Impromptu everyday disclosure dances: how women with fibromyalgia respond to disclosure risks at work. Disabil Rehabil. [Nov 27 Epub ahead of print.] "Women with fibromyalgia and other stigmatized illnesses improvised everyday disclosures when they needed to explain fluctuating work ability, when others needed reminding about invisible impairments, and when workplace relationships changed. These impromptu disclosures comprised three dimensions: exposing oneself to scrutiny by disclosing both illness and impairments, divulging stigmatized illness, and revealing invisible impairments selectively….Through impromptu disclosure dances, women tailored disclosure to changing immediate circumstances. While assumptions from psychological theories of risk underlie current conceptualizations of disclosure as planned in advance, this article examines disclosure through a different lens: social theories of everyday risk. Implications for rehabilitation for women with fibromyalgia, disclosing illness and impairments at work may entail risks to their jobs and workplace relationships. Rehabilitation professionals need to consider these risks when advising women with fibromyalgia about disclosing their illness and impairments at work. Professionals may first want to learn from clients about their workplace cultures and relationships, and their perceptions of disclosure risk. Professionals can then suggest a range of disclosure responses, depending on the relationship and risk."

Olesiejuk M, Marusiak J, Chalimoniuk M. Myofascial trigger points therapy decreases myotonometric tone and stiffness of trapezius muscle, benefits headaches and muscle pain in migraine. NeuroRehabilitation. 2023;52(2):299-310. "Studies have shown that 93% of people with migraine have an increased number of active Ischemic Compression Myofascial Trigger Points (IC-MTrPs) therapy…. IC-MTrPs therapy resulted in a decrease of upper trapezius muscle tone and stiffness, with simultaneous alleviation of shoulder girdle and neck muscle pain and the headaches characteristics in episodic migraine patients without aura.

Olfson M, Wall M, Liu SM et al. 2018. Insomnia and impaired Quality of Life in the United States. J Clin Psychiatry. 79(5). "Insomnia is prevalent and associated with substantial population-level burden in self-assessed health. The co-occurrence of insomnia with common medical conditions is differentially related to pain and to a lesser extent to stressful life events and mental disorders."

Oliveira P, Costa ME. 2009.  Interrelationships of adult attachment orientations, health status and worrying among fibromyalgia patients.  J Health Psychol. 14(8):1184-1195.

Oliveira-Campelo NM, de Melo CA, Alburquerque-Sendín F et al. 2013. Short- and Medium-Term Effects of Manual Therapy on Cervical Active Range of Motion and Pressure Pain Sensitivity in Latent Myofascial Pain of the Upper Trapezius Muscle: A Randomized Controlled Trial. J Manipulative Physiol Ther. [Jun 11 Epub ahead of print]. "Manual techniques on upper trapezius with latent trigger point seemed to improve the cervical range of motion and the pressure pain sensitivity. These effects persist after 1 week in the IC (ischemic compression) group."

Oliven A, Odeh M. 2006.  Effect of positional changes of anatomic structure on upper airway dilating muscle shortening during electro- and chemostimulation.  J Appl Physiol 101(3):745-751.   “...positional alterations of anatomic structures in the neck have a dramatic effect on the magnitude of shortening of the activated GG (genioglossus) and GH (geniohyoid), which may reduce substantially their ability to protect pharyngeal patency.”  [TrPs in some muscles may affect upper airway function. DJS]

Oliver JE, Carlson C. 2020. Misperceptions about the 'Opioid Epidemic:' Exploring the facts. Pain Manag Nurs. 21(1):100-109. "A plethora of statistics and claims exist concerning the rise in prescription opioid use and the increase in opioid-related deaths. Eleven misperceptions were identified that underlie some of the growing national concern and backlash against opioid use. Misperceptions include the number of opioid overdose deaths, the quality of government-sponsored data and guidelines, the impact of opioid dose escalation on overdose risk, postoperative opioid use associated with long-term use, and the link between prescription opioid use and heroin initiation. Implications for research, practice and education include (a) a call for improvement in data recording, (b) unbiased and clear reporting of information, (c) a call for health care providers to ask critical questions when presented with data, and (d) a call for policymakers to avoid unnecessarily restrictive practices that are founded in fear and may cause unintended harm to patients in pain."

Olivier B, Pramod A, Maleka D. 2018. Trigger point sensitivity is a differentiating factor between cervicogenic and non-cervicogenic headaches: A cross-sectional, descriptive study. Physiother Can. 70(4):323-329. "A common factor in all forms of headache is the presence of myofascial trigger points (TrPs). The aim of this study was to compare the presentation of patients with cervicogenic headaches and patients with non-cervicogenic headaches in the sensitivity of TrPs in their upper trapezius, sternocleidomastoid, temporalis, and posterior cervical muscles." This study from South Africa found: "Increased sensitivity of TrPs in the upper trapezius muscle may be used as a differentiating factor in the diagnosis of cervicogenic headaches. This finding emphasizes the importance of integrating this muscle into the rehabilitation programs of patients with cervicogenic headache."

Olsen MN, Sherry DD et al. 2013. Relationship between sleep and pain in adolescents with Juvenile Primary Fibromyalgia Syndrome. Sleep. 36(4): 509–516. "Although ADS (alpha-delta sleep) has been less well studied in children, it also appears to be associated with JPFS. Roizenblatt and colleagues found significantly more ADS in both children and mothers with fibromyalgia than in healthy controls, similar to our results. Also consistent with our findings, they observed significantly poorer sleep efficiency and more arousals in children with JPFS than in controls. ADS was significantly associated with the number of tender points and inversely related to pain threshold in both children and mothers with fibromyalgia, a correlation we expected to find but did not observe. In our study, pain improved significantly after treatment but the amount of ADS did not change, suggesting these constructs may not be causally related. Though further study is clearly indicated, our results suggest that the etiologies of pain and ADS may be independent in JPFS…. The efficacy of exercise therapy in treating fibromyalgia is well documented. It has been shown to improve sleep in adult patients, although whether it affects sleep architecture is unknown…. Our findings do not support the idea that exercise therapy for pain improves sleep quality by reducing ADS. ADS was not correlated with subjective sleep difficulty and persisted in the absence of reports of unrefreshing sleep. The prevalence of ADS in our sample was high at baseline and, despite significant improvements in subjective sleep quality and physical fitness, did not change after treatment…. It is worth emphasizing that ADS is not specific to fibromyalgia. ADS has been observed in patients with chronic fatigue syndrome as well as in healthy individuals. It is possible that, rather than pain causing ADS (or vice versa), some other factor, such as genetics, predisposes some individuals to chronic pain, ADS, or both."

Olsen RV, Andersen HH, Moller HG et al. 2014. Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM8 and TRPA1 using topical L-menthol and trans-cinnamaldehyde in healthy volunteers. Eur J Pain. [Mar 25 Epub ahead of print.] "This study elucidates the potential of L-menthol as a counter-irritant to secondary neurogenic inflammation and provides evidence of an intricate interplay between cold receptors TRPA1 and TRPM8, warranting further investigation of the neural coding of cold pain perception."

Olsen Y, Daumit GL. 2004.  Opioid prescribing for chronic nonmalignant pain in primary care: challenges and solutions.  Adv Psychosom Med 25:138-150.

Oluwasanmi OJ, Mckenzie DA, Adewole IO et al. 2019. Postpolio syndrome: A review of lived experiences of patients. Int J Appl Basic Med Res. 9(3):129-134. "Postpolio syndrome (PPS) refers to a group of conditions that are present in patients, years after recovery from initial acute paralytic poliomyelitis. About 15%-80% of 20 million polio survivors worldwide will experience exacerbation of symptoms which typically appear 15-30 years after the resolution of initial poliomyelitis. Symptoms include new muscle weakness, fatigue, myalgia, joint pain, dysphagia, and difficulty breathing. Other reported symptoms include cold intolerance, sleep disorder, dysphonia, loss of stamina, musculoskeletal deformities, cardiovascular disorders, psychosocial problems, and restless legs syndrome. These symptoms are attributed to the superimposed neuronal loss of aging with inflammatory mechanisms, but without any convincing evidence of viral reactivation. Risk factors include female gender, respiratory symptoms, normal aging, permanent disability caused by motor neuron damage, muscle overuse and disuse, aging, and immunologic mechanisms. Hypothyroidism-induced myopathy and fibromyalgia are a differential diagnosis for PPS, and exclusion diagnosis is required as confirmatory criteria for PPS. The symptoms of PPS presented determine the course of management."

Oncu J, Basoglu F, Kuran B. 2013. A comparison of impact of fatigue on cognitive, physical, and psychosocial status in patients with fibromyalgia and rheumatoid arthritis. Rheumatol Int. [Jul 24 Epub ahead of print]. This study from turkey found "Fatigue has different impacts on QoL (quality of life) in FM and RA, respectively. Together with pain, fatigue leads FM patients to see disease as having worse health in terms of mental function, whereas it leads to poor health in terms of physical function in RA."

Onder H, Hamamci M, Alpua M et al. 2019. Comorbid fibromyalgia in migraine patients: clinical significance and impact on daily life. Neurol Res. Jun 20:1-7. [Epub ahead of print] "The results of our study may suggest the presence of FM as a clinical sign of a more severe migraine. However, the long-term prospective studies including these groups of patients are needed to understand the prognostic impact and importance of the comorbid FM in migraine."

Orellana C, Gratacos J, Galisteo C et al. 2009.  Sexual dysfunction in patients with fibromyalgia.  Curr Rheumatol Rep. 11(6):437-442.  “Several studies have investigated sexual function in patients with fibromyalgia (FM).  All reports agree that sexual function seems frequently impaired in this condition.  This dysfunction is usually severe and may affect all domains of sexuality.  Given the complexity of factors involved in human sexual function and the intricacy of the physiopathology of FM, many factors and mechanisms have been implicated.  Per our literature review, depression may be the main contributing factor to FM-related sexual dysfunction.  However, prospective studies are needed, as reports have lacked sufficient quality to draw definitive conclusions.  Recognition of sexual dysfunction and its inclusion in multidisciplinary management are needed to improve quality of life for patients with FM.”  [It is greatly to be hoped that future research will consider that much of these symptoms attributed to FM are actually due to co-existing TrPs, well-documented as causing sexual dysfunction in both male and female patients.  DJS]

Orenstein, S. R. 1994. The prone alternative. Pediatrics 94(1):104-5.

Orenstein, S. R., H. H. Magill and P. Brooks. 1987. Thickening of infant feedings for therapy of gastroesophageal reflux. J Pediatr 110(2):181-6.

Orhurhu VJ, Pittelkow TP, Hooten WM. 2015. Prevalence of smoking in adults with chronic pain. Tob Induc Dis. 13(1):17. "The prevalence of smoking in patients with chronic pain has not declined when compared to the general population. The higher prevalence of smoking was consistently observed in commonly occurring pain diagnoses including fibromyalgia, back pain, and headache." Free PMC Article

Orlandi AC, Ventura C, Gallinaro AL et al. 2012. Improvement in pain, fatigue, and subjective sleep quality through sleep hygiene tips in patients with fibromyalgia. Rev Bras Reumatol. 52(5):672-678. "The sleep hygiene instructions allowed changing the patients' behavior, which resulted in pain and fatigue improvement, increased subjective quality of sleep, in addition to facilitating falling asleep after waking up in the middle of the night."

Ormandy L. 1994. Scapulocostal syndrome.  Va Med Q. 121(2):105-108.  Much deep pain in the scapular region may be helped by “...infiltrating a trigger point in the subscapularis region of the medical aspect of the scapular spine (root of the scapular spine) with a mixture of 2cc plain 1% lidocaine hydrochloride...plus 1 cc beta-methasone sodium phosphate and acetate suspension...followed by physical therapy exercises.  190 patients (43.19%) received one block, 175 (39.77%) received two blocks, and 75 (17.04%) received three blocks.  Upon completion of treatment, 97.7% of the patients were relieved of their discomfort and returned to their original occupation.”  [Since this was published, one must wonder how many patients with similar symptoms have been subjected to unnecessary surgery.  DJS]

Orstavik K, Norheim I, Jorum E. 2006.  Pain and small-fiber neuropathy in patients with hypothyroidism.  Neurology 67(5):786-791.  “Some patients treated for hypothyroidism have symptoms and findings compatible with small-fiber neuropathy or ‘hyperphenomena’ indicating central sensitization.”  This is another study showing a link between FMS and hypothyroid.

Ortancil O, Sanli A, Eryuksel R et al. 2010. Association between serum ferritin level and fibromyalgia syndrome. Eur J Clin Nutr. [Jan 20 Epub ahead of print]  “Iron is essential for a number of enzymes involved in neurotransmitter synthesis. Analysis of cerebrospinal fluid in fibromyalgia syndrome (FMS) has shown a reduction in the concentration of biogenic amine metabolites, including dopamine, norepinephrine and serotonin…. A total of 46 patients with primary FMS participated in this case-control study, and 46 healthy females who were age matched to the patients were used as the control group….Our study implicates a possible association between FM and decreased ferritin level, even for ferritin in normal ranges. We suggest that iron as a cofactor in serotonin and dopamine production may have a role in the etiology of FMS.”  [Decreased muscle ferritin level is also a perpetuating factor for TrPs, and TrPs often maintain FM central sensitization. One must be careful, however, as increased iron in post-menopausal women can increase cholesterol levels. For people with multiple co-existing interactive conditions it is not easy. DJS]

Ortega E, García JJ, Bote ME et al. 2009. Exercise in fibromyalgia and related inflammatory disorders: known effects and unknown chances. Exerc Immunol Rev. 15:42-65. "The results confirm an elevated 'inflammatory status' in the FM syndrome and strengthen the hypothesis that the benefits of exercise in FM patients are mediated, at least in part, by its anti-inflammatory effects. A better regulation of the cytokine-HPA axis feedback may be also involved."

Ortega-Santiago R, de-la-Llave-Rincon AI, Laguarta-Val S et al. 2012. [Neurophysiological advances in carpal tunnel syndrome: process of central sensitization or local neuropathy]. Rev Neurol. 54(8):490-496. [Spanish] "Several studies…support the presence of a complex process of peripheral and central sensitization in patients with CTS which may constitute a negative prognosis factor for the management of these patients….The advances in neurosciences in the last years support the presence of peripheral and central sensitization mechanisms in CTS. These mechanisms justify the necessity of conceptual changes and in the management, both conservative and surgical, of this syndrome. Additionally, central sensitization can also play a relevant role in the prognosis of CTS since it can constitute a negative prognosis factor for its treatment.

Ortiz R, Ballard ED, Machado-Vieira R et al. 2016. Quantifying the influence of child abuse history on the cardinal symptoms of fibromyalgia. Clin Exp Rheumatol. [Jan 8 Epub ahead of print.] From the US National Institutes of Health: "…the experience of child abuse is associated with FM symptom severity and may shape the biological development of interoception in ways that predispose to pain and polysymptomatic distress."

Ortiz-Comino L, Fernandez-Lao C, Castro-Martin E et al. Myofascial pain, widespread pressure hypersensitivity, and hyperalgesia in the face, neck, and shoulder regions, in survivors of head and neck cancer. Support Care Cancer. 2019 Nov 21. [Epub ahead of print] "Medical treatment for head and neck cancer may induce the presence of inflammation, pain, and dysfunction. The purpose of the current study was to assess the presence of myofascial trigger points (TrPs) and their relationship with widespread pressure hypersensitivity and hyperalgesia in survivors of head and neck cancer (sHNC).... The sHNC had more TrPs in all muscles on the affected side (p < 0.05) than did the healthy controls, and in the temporalis, masseter, and suboccipitalis muscles on the unaffected side.... The intensity of cervical pain correlated positively with the presence of upper trapezius TrPs.... sHNC suffering cervical and/or temporomandibular joint pain have multiple active TrPs and experience widespread pressure hypersensitivity and hyperalgesia, suggestive of peripheral and central sensitization."

Ortiz-Rubio A, Torres-Sanchez I, Cabrera-Martos I et al. 2021. Respiratory disturbances in fibromyalgia: A systematic review and meta-analysis of case control studies. Expert Rev Respir Med. Apr 26;1-11. "Persons with fibromyalgia experience respiratory disturbances, such as reduced chest expansion, maximum expiratory pressure, maximum inspiratory pressure, and maximal voluntary ventilation. [No assessment for co-existing MTrPs in the respiratory muscles, which can affect those values. Previous positive studies also did not allow for co-existing conditions, including the consequences of introducing less oxygenation to muscles already deprived of oxygen by TrPs blood vessel entrapment. DJS]

Osborne NJ, Gatt IT. 2010. Management of shoulder injuries using dry needling in elite volleyball players. Acupunct Med. 28(1):42-45. “These case reports describe the short-term benefits of dry needling in shoulder injuries in four international female volleyball athletes during a month-long intense competitive phase, using both replicable subjective and objective measures. Dry needling of scapulohumeral muscles was carried out. Range of movement, strength and pain were assessed before and after treatment, with a functional assessment of pain immediately after playing and overhead activity, using the short form McGill Pain Questionnaire. All scores were improved post-treatment and athletes were able to continue overhead activities. Previous studies have suggested that myofascial trigger points may cause significant functional weakness and reduced range of motion, with referred pain. Trigger point dry needling has been successful in treating athletes with myofascial pain and impingement symptoms but with only subjective improvement and not during a competitive phase. These cases support the use of dry needling in elite athletes during a competitive phase with short-term pain relief and improved function in shoulder injuries. It may help maintain rotator cuff balance and strength, reducing further pain and injury.”  [Although this study was done on volleyball players, it can be extrapolated to professional sports.  Considering the amount of money involved with athletes and the invasiveness, expense and sometimes career-limiting effect of surgery, it is certainly in the interest of the insurance companies to become proficient in the field of myofascial pain.  Right now the reimbursement system doesn’t cover many myofascial treatments, but does cover the surgery, and this must be changed. Many rotator cuff and other soft tissue injuries could be treated effectively and risk of further injury minimized if the trigger points were treated. DJS] 

O’Shaughnessy, T. 1994. Craniomandibular/temporomandibular/cervical implications of a forced hyper-extension/hyper-flexion episode (ie., whiplash). Funct Orthod 11(2):5-10, 12.

Ostensen, M., A. Rugelsjoen and S. H. Wigers. 1997. The effect of reproductive events and alterations of sex hormone levels on the symptoms of fibromyalgia. Scand J Rheumatol 26(5):355-360.

Ostrovsky DA. 2018. Tai Chi may be more effective for improving fibromyalgia symptoms than aerobic exercise. Explore (NY). [Aug 6 Epub ahead of print]

Otadi K, Hadian MR, Talebian S et al. 2013. The effect of myofascial neck pain on postural control: visual deprivation. J Back Musculoskelet Rehabil. 26(4):375-380. "Our results showed that myofascial neck pain syndrome might be one of the disturbing factors on standing balance."

Otani K, Kikuchi S. 2005.  [Block treatment for low back pain-Technical note.]  Clin Calcium 15(3):437-441. [Japanese]  Trigger point block is one of the common procedures discussed in this paper on low back pain.

Otis J, Rothman M. 2006.  A Phase III study to assess the clinical utility of low-dose fentanyl transdermal system in patients with chronic nonmalignant pain.  Curr Med Res Opin. 22(8):1493-1501.  This lower-dose fentanyl may be of benefit to opioid-naive patients and the elderly.  It had a beneficial therapeutic effectiveness with a lessened drop out rate.

Ottman AA, Warner CB, Brown JN. 2018. The role of mirtazapine in patients with fibromyalgia: a systematic review. Rheumatol Int. [Jun 2 Epub ahead of print] "Mirtazapine is commonly used to treat major depressive disorder. Due to its effects on multiple neurotransmitters, it has been investigated for possible benefits in patients with fibromyalgia.... In patients with fibromyalgia, treatment with mirtazapine resulted in improvements in pain, sleep, and quality of life. Study durations ranged from 6 to 13 weeks and studies used varying dosing strategies for mirtazapine. Minor occurrences of somnolence, weight gain, nasopharyngitis, dry mouth, and increased appetite were reported with mirtazapine use. Based on the reviewed literature, mirtazapine appears to be a promising therapy to improve pain, sleep, and quality of life in patients with fibromyalgia. These benefits were demonstrated in patients that were treatment naïve and those that had failed previous therapies. Additional clinical evidence through larger and longer length trials would be of benefit to further define the role of mirtazapine for patients with fibromyalgia."

Ou SC, Lin MC, Lin HJ et al. 2020. Association between erectile dysfunction and fibromyalgia in male patients: A Taiwanese nationwide population-based cohort study. Int J Urol. Sep 9. Online ahead of print. "The Cox proportional hazards regression analysis showed increased risk of erectile dysfunction in the fibromyalgia cohort regardless of treatment prescriptions of tramadol, antidepressants, gabapentin and non-steroidal anti-inflammatory drugs… Fibromyalgia was found to be an independent risk factor for the incidence of erectile dysfunction". Patients were not screened for MTrPs that can cause ED. DJS]

Ouyang A, Wrzos HF. 2006.  Contribution of gender to pathophysiology and clinical presentation of IBS: should management be different in women?  Am J Gastroenterol. 101 Suppl 3:S602-609.

Overman CL, Kool MB, Da Silva JA et al. 2015. The prevalence of severe fatigue in rheumatic diseases: an international study. Clin Rheumatol. 2015 Aug 15. [Epub ahead of print] "Fatigue is a common, disabling, and difficult-to-manage problem in rheumatic diseases…. Severe fatigue was present in 41 to 57 % of patients with a single inflammatory rheumatic disease such as rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, Sjögren's syndrome, psoriatic arthritis, and scleroderma. Severe fatigue was least prevalent in patients with osteoarthritis (35 %) and most prevalent in patients with fibromyalgia (82 %)…. one out of every two patients with a rheumatic disease is severely fatigued. As severe fatigue is detrimental to the patient, the near environment, and society at large, unraveling the underlying mechanisms of fatigue and developing optimal treatment should be top priorities in rheumatologic research and practice."

Ovrom EA, Mostert KA, Khakhkhar S, et al. A comprehensive review of the genetic and epigenetic contributions to the development of fibromyalgia. Biomedicines. 2023 Apr 7;11(4):1119. "Although there is no single gene that results in the development of FM, this study reveals that there is no single gene that results in the development of FM, this study reveals that certain polymorphisms in genes involved in the catecholaminergic pathway, the serotonergic pathway, pain processing, oxidative stress, and inflammation may influence susceptibility to FM and the severity of its symptoms. Furthermore, epigenetic changes at the DNA level may lead to the development of FM. Likewise, microRNAs may impact the expression of certain proteins that lead to the worsening of FM-associated symptoms."

Ozbayrak SS, Battal H, Gokpinar HH, et al. 2021. Facial emotion recognition ability in patients with fibromyalgia. Clin Ter. Nov 22;172(6):547-551. "We hypothesize that fibromyalgia patient recognize negative emotions more than positive emotions…. This study provides evidence of impairment in sad facial emotions and more response time for happy, angry, neutral and surprised facial emotions. These may cause poor interpersonal relationship and insufficient social functioning and leading to chronicity of the disease."

Ozcan OU, Ozcan DS, Candemir B et al. 2015. Evaluation of aortic elastic properties in patients with fibromyalgia. Int Angiol. [Feb 12 Epub ahead of print.] This study "…suggest that elastic properties of aorta are impaired in patients with severely symptomatic fibromyalgia."

Ozden MC, Atalay B et al. 2018. Efficacy of dry needling in patients with myofascial temporomandibular disorders related to the masseter muscle. Cranio. 9:1-7. [Epub ahead of print] "This randomized, single-center clinical trial aimed to compare the efficacy of superficial dry needling (SDN) and deep dry needling (DDN) in patients with myofascial temporomandibular disorder (MTMD) related to the masseter muscle [trigger points].... SDN showed better pain-reduction efficacy in patients with MTMD. Further research with a larger size sample and a longer follow-up period will help elucidate the benefits of SDN."

Ozel HE, Ozkiris M, Gencer ZK et al. 2013. Audiovestibular functions in noninsulin-dependent diabetes mellitus. Acta Otolaryngol. [Oct 16 Epub ahead of print]. "This study supports the proposition that vestibular dysfunction and sensorineural hearing loss (SNHL) may be considered among the complications due to noninsulin-dependent diabetes mellitus (NIDDM)….Hearing thresholds in all frequencies (except at 500 Hz for bone conduction) and SRS values were statistically significant in patients with NIDDM and control subjects, but there was no statistically significant difference according to the duration of the disease. Statistically significant alterations were present in VFT in patients with NIDDM compared with the control subjects."

Ozen T, Tonga E, Polat MG et al. 2020. Cervical proprioception accuracy is impaired in patients with axial spondyloarthritis. Musculoskelet Sci Pract. Nov 16;51:102304. "Cervical proprioception accuracy is impaired in patients with axSpA. It seems that controlling disease activity by using appropriate medication may have a positive effect on cervical proprioception accuracy." [It would be interesting to assess these patients for SCM and other area TrPs. TrPs frequently accompanied axSpA, and the TrPs could be a treatable cause of the proprioception dysfunction. DJS]

Ozgocmen, Salih. 2005.  New strategies in evaluation of therapeutic efficacy in fibromyalgia syndrome.  Current Pharmaceutical Design [November Epub ahead of print].  “The use of multiple outcome variables reflecting the complexity of FM and co-morbid syndromes makes it difficult to evaluate the efficacy or effectiveness of the treatment in clinical trials.  Additionally, researchers inevitably rely on patients’ self-reported outcome data, which is prone to error and bias.”  “Clinicians and researchers now have various highly validated and adequate outcome domains to assess FM symptoms and new researches continue to add new valuable domains.  Nevertheless the current problem is to conclude which treatment works best for whom and which are the outcome domains suitable for FM patients or patients’ subgroups with different prominent features.  Standardized and appropriate core outcome domains for FM clinical trails will encourage more complete investigations, relevant outcome reporting and well-designed multicenter trials.”

Ozgocmen S, Ozyurt H., Sogut S et al. 2005.  Antioxidant status, lipid peroxidation, and nitric oxide in fibromyalgia: etiologic and therapeutic concerns.  Rheumatol Int. Nov 10:1-10.  [Epub ahead of print]  This article offers several possible therapeutic avenues for fibromyalgia treatment by indicating possible metabolic subsets.

Ozgocmen, S, Ardicoglu O, Lipid Profile in Patients with Fibromyalgia and Myofascial Pain Syndromes, Yonsei Medical Journal 41(5):541-545, 2000. Significant changes to the lipid profile seems to be part of the myofascial component rather than the fibromyalgia component when these conditions occur together.

Ozkan F, Cakir Ozkan N, Ekorkmaz U. 2011. Trigger point injection therapy in the management of myofascial temporomandibular pain. Agri 23(3):119-125. "Myofascial pain is the most common temporomandibular disorder.....Our results indicate that trigger point injection therapy combined with splint therapy is effective in the management of myofascial TMD pain. " Further research is needed. [One must be careful with splint use in TrPs, as immobility is a perpetuating factor of TrPs. One needs to treat all the TrPs affecting the TMJ, including the soleus. Unless one knows all TrPs, one may not know to check the calf for TrPs that can affect the jaw. DJS]

Ozturk G, Kulcu DG, Mesci N et al. 2016. Efficacy of kinesio tape application on pain and muscle strength in patients with myofascial pain syndrome: a placebo-controlled trial. J Phys Ther Sci. 28(4):1074-1079. Patients with myofascial pain syndrome receiving an application of Kinesio taping exhibited statistically significant improvements in pain and upper trapezius muscle strength. Free PMC Article [The tape seems to help patients with a few trigger points, especially athletes. Perhaps it might be a useful aid to help some of the worst trigger points in patients with CMPD. We need more research on this. DJS]

Oztürk O, Tek M, Seven H. 2012. Temporomandibular disorders in scuba divers - an increased risk during diving certification training. J Craniofac Surg. 23(6):1825-1829. The design and fit of a mouthpiece on SCUBA can increase the risk of developing TMJD and TrPs as the diver is constantly struggling to attain mouthpiece stability.

Pace JB, Nagle D. 1976.  Piriform syndrome. West J Med. 124(6):435-439.  Piriformis TrPs are often mistaken as discogenic pain, causing unnecessary pain, cost and delay of adequate treatment.  Symptoms can include female dyspareunia, low back pain and hip pain radiating down the leg, and muscle weakness.

Pachas WN, Bekken KN. 2007.  Development of fibromyalgia syndrome following traumatic brain injury.  J Musculoskel Pain 15 (Supp 13):56 item 100.  [Myopain 2007 Poster]  “In all patients there was a clear relationship between the time of their TBI (traumatic brain injury) and subsequent FMS.”   “The factors involved in TBI as the cause or as an initiating factor of FMS are unknown.  Our data suggest that there might be a connection between these disorders.”

Pachas WN, Bekken KN. 2007.  The role of memantine in the treatment of the memory dysfunction of patients with fibromyalgia syndrome.  J Musculoskel Pain 15 (Supp 13):42 item 73.  [Myopain 2007 Poster]  “Memantine improves memory and function in patients with Alzheimer’s.  The possibility that FMS patients may also benefit was explored in this trial.”  “Sixteen patients were treated with memantine, 3 patients did not improve.  The other patients had moderate to excellent response, some were able to return to work and most felt marked improvement in the quality of life.  Neuropsychological testing reflected some of these changes.”  “Memantine is an N-methyl-D-aspartic acid receptor antagonist.”  “Some of the patients on this trial had a remarkable improvement in their memory and could not function without it.  However, double-blind placebo-controlled studies should define the value of memantine in FMS.”

Pacheco-Barrios K, Lima D, Danielle Pimenta, et al. Motor cortex inhibition as a fibromyalgia biomarker: a meta-analysis of transcranial magnetic stimulation studies. Brain Netw Modul. 2022 Apr-Jun;1(2):88-101. "The main findings were: (1) fibromyalgia subjects present less intracortical inhibition…and higher resting motor thresholds…when compared to controls; (2) interventions such as exercise, pregabalin, and non-invasive brain stimulation increased intracortical inhibition…and cortical silent period, when compared to placebo or sham stimulation; (3) changes on intracortical excitability are correlated with clinical improvements - higher inhibition moderately correlates with less pain, depression, and pain catastrophizing; lower facilitation moderately correlates with less fatigue. Measures of intracortical inhibition and facilitation indexed by TMS are potential diagnostic and treatment response biomarkers for fibromyalgia subjects. The disruption in the intracortical inhibitory system in fibromyalgia also provides additional evidence that fibromyalgia has some neurophysiological characteristics of neuropathic pain. Treatments inducing an engagement of sensorimotor systems (e.g., exercise, motor imagery, and non-invasive brain stimulation) could restore the cortical inhibitory tonus in FM and induce clinical improvement."

Padamsee M, Mehta N, White GE. 1987.  Trigger point injection: a neglected modality in the treatment of TMJ dysfunction.  J Pedod. 12(1):72-92.

Pagotto U, Marsicano G, Cota D et al. 2005.  The emerging role of the endocannabinoid system in endocrine regulation and energy balance.  Endocr Rev. [Nov 23 Epub ahead of print]   [The role of the endocannabinoid system includes the modulation of all the endocrine hypothalamic-peripheral endocrine axes, control of reproduction and sexual behavior, control of appetite and energy balance and other  metabolic areas that are often imbalanced in FMS. DJS]

Pai RS, Vas L. 2018. Ultrasound-guided intra-articular injection of the radio-ulnar and radio-humeral joints and ultrasound-guided dry needling of the affected limb muscles to relieve fixed pronation deformity and myofascial issues around the shoulder, in a case of Complex Regional Pain Syndrome Type 1. Pain Pract. 18(2):273-282. "Complex regional pain syndrome (CRPS) occurs due to different pathophysiological mechanisms. Presently there is no description of definitive treatment that can resolve the especially recalcitrant motor issues of disability in CRPS type 1 (CRPS-1)….In this patient with CRPS-1, intra-articular injections with steroid reduced nociception in the affected local structures and sensitization in the nervous system; dry needling resolved the myofascial issues; sustained physiotherapy maintained the motor recovery; and behavioral therapy techniques addressed the cognitive and life stress issues. It was concluded that the presenting symptoms in this case were a consequence of interactions between humoral, nervous, and myofascial systems."

Painter JT, Crofford LJ, Talbert J. 2013. Geographic variation of chronic opioid use in fibromyalgia. Clin Ther. 35(3):303-311. "Opioid use for the treatment of chronic nonmalignant pain has increased drastically over the past decade. Although no evidence of efficacy exists supporting the treatment of fibromyalgia (FM) with chronic opioid therapy, a large number of patients are receiving this therapy....Geographic variation in chronic opioid use among patients with FM exists at rates similar to those seen in other studies examining opioid use. This large level of geographic variation suggests that the prescribing decision is not based solely on physician-patient interaction but also on contextual and structural factors at the state level. The level of physician and condition prevalence suggest that information dissemination and peer-to-peer interaction may play a key role in adopting evidence-based medicine for the treatment of patients suffering from FM and related conditions. Level of diagnosis prevalence as a predictor of evidence-based practice has not been reported in the literature and is an important contribution to research on geographic variation."

Pal JS, Desai J, Bajwa Z. 2007.  Superior oblique muscle deinnervation: implications for differential innervation of myofascial trigger points.  J Musculoskel Pain 15 (Supp 13):66 item 117.  [Myopain 2007 Poster]  “SOM (superior oblique muscle) TrPs may be a cause, as opposed to a consequence, of headache.”  “Eye movement disorders increase risk for headache due to awkward head tilts and double vision.”

Palacios-Cena M, Barbero M, Falla D et al. 2017. Pain extent is associated with the emotional and physical burdens of chronic tension-type headache, but not with depression or anxiety. Pain Med. [Apr 6 Epub ahead of print] "Earlier studies suggest that pain extent, extracted from the patients' pain drawings, can help clinicians to identify people with central sensitization or worse clinical features. Our aim was to investigate possible associations between perceived pain extent and clinical pain features, burden of headache, psychological outcomes, and pressure sensitivity in people with chronic tension-type headache (CTTH)…. Pain extent weakly correlated with older age as well as with higher emotional and physical burden of the headache in CTTH. In this population, there was no relationship between pain extent and PPT, indicating that larger pain areas were not associated with signs of central sensitization. Pain drawings can complement other clinical pain features for better characterization of CTTH, but further studies are needed."

Palacios-Cena M, Ferracini GN, Florencio LL et al. 2017. The number of active but not latent trigger points associated with widespread pressure pain hypersensitivity in women with episodic migraines. Pain Med. 18(12):2485-2491."Previous studies suggest that trigger points (TrPs) contribute to migraine pain, but no data is available on the effects of TrPs on pressure pain sensitivity.... Active and latent TrPs were bilaterally explored in the temporalis, masseter, suboccipital, sternocleidomastoid, upper trapezius, and splenius capitis musculature. Pressure pain thresholds (PPTs) were assessed over the trigeminal area (i.e., temporalis muscle), extratrigeminal (i.e., C5/C6 zygapophyseal joint), and a distant pain-free point (i.e., tibialis anterior muscle)....Active TrPs in the temporalis and upper trapezius muscles were the most prevalent. The number of active but not latent TrPs was significantly and negatively associated with PPTs: the higher the number of active TrPs, the lower the widespread PPT and the more generalized sensitization."

Pallanti S, Porta F, Salerno L. 2020. Adult attention deficit hyperactivity disorder in patients with fibromyalgia syndrome: Assessment and disabilities. J Psychiatr Res. Oct 24;S0022-3956(20)31030-X. "Overall, results suggest that ADHD can increase burden adding specific disability in work and social activities, and it is associated with a trend for the excessive use of opioid painkillers. Detection of neurodevelopmental and actual symptoms of ADHD is highly recommended especially in patient prone to increase the dose of anti-pain medication." [It is logical to assess patients for co-existing conditions. DJS]

Palmer S, Bailey J, Brown C et al. 2019. Sensory function and pain experience in arthritis, complex regional pain syndrome, fibromyalgia syndrome and healthy volunteers: A cross-sectional study. Clin J Pain. [Aug 12 Epub ahead of print] "People with FMS and CRPS demonstrate extensive sensory dysfunction. Arthritis patients had sensory profiles closer to healthy participants. LTT (light touch threshold) may provide a clinically relevant and accessible assessment for CRPS."

Palmio J, Sandell S, Hanna MG et al. 2017. Predominantly myalgic phenotype caused by the c.3466G>A p.A1156T mutation in SCN4A gene. Neurology. [Mar 22 Epub ahead of print.] "The main clinical manifestation in p.A1156T patients was not myotonia or periodic paralysis but exercise- and cold-induced muscle cramps, muscle stiffness, and myalgia. EMG myotonic discharges were detected in most but not all. Electrophysiologic compound muscle action potentials exercise test showed variable results. The p.A1156T mutation was identified in one patient in the DM2-neg group but not in the fibromyalgia group, making a total of 30 patients so far identified. Functional studies of the p.A1156T mutation showed mild attenuation of channel fast inactivation…. The unspecific symptoms of myalgia stiffness and exercise intolerance without clinical myotonia or periodic paralysis in p.A1156T patients make the diagnosis challenging. The symptoms of milder SCN4A mutations may be confused with other similar myalgic syndromes, including fibromyalgia and myotonic dystrophy type 2." [Those with exercise- and cold-induced muscle cramps, muscle stiffness, and muscle aches or have patients with the same might want to consider this possibility. DJS]

Palomino RA, Nicassio PM, Greenberg MA et al. 2007.  Helplessness and loss as mediators between pain and depressive symptoms in fibromyalgia.  Pain. [Feb 28 Epub ahead of print]  “The findings confirm the importance of helplessness and demonstrate that the cognitive meaning of having FM plays a more central role in predicting depressive symptomatology than illness-related stressors, such as pain or disability.”

Palstam A, Gard G, Mannerkorpi K. 2013. Factors promoting sustainable work in women with fibromyalgia. Disabil Rehabil. [Jan 22 Epub ahead of print]. "Promoting factors for work were identified, involving individual and environmental factors. These working women with FM had developed advanced well-functioning strategies to enhance their work ability. The development of such strategies should be supported by health-care professionals as well as employers to promote sustainable work in women with FM… Working women with FM appear to have developed advanced well-functioning individual strategies to enhance their work ability. The development of individual strategies should be supported by health-care professionals as well as employers to promote sustainable work and health in women with FM."

Pamfil C, Choy EHS. 2018. Functional MRI in rheumatic diseases with a focus on fibromyalgia. Clin Exp Rheumatol. 36 Suppl 114(5):82-85. "Pain is the most common symptom in rheumatic diseases. However, the severity of pain does not correlate with pathology. The lack of an objective test for pain results in clinicians consider pain in patients with fibromyalgia as psychological. Research over the last two decade using functional neuroimaging especially functional MRI scan have demonstrated objectively that patients with fibromyalgia were not malingering. Pain processing is complex and multiple regions of the brain are involved. One consistent finding is decrease activity in regions of the brain involved in pain inhibitory pathways suggesting this is one of the fundamental pathophysiology processes in fibromyalgia." Free Article

Pan Y, Jiang L, Wang C. The impact of N-cadherin-β-catenin signaling on the analgesic effects of glial cell-derived neurotrophic factor in neuropathic pain. Biochem Biophys Res Commun. 2019 Nov 25. [Epub ahead of print] "Long-term neuropathic pain can lead to anxiety, depression, and other issues, which seriously affect patients' quality of life. For this reason, it is important to find effective treatments. Studies have shown that glial cell-derived neurotrophic factor (GDNF) can relieve neuropathic pain. However, its mechanism of action is unknown. Our previous study of GDNF suggested that the N-cadherin-β-catenin transmembrane signaling system might play a role in GDNF transmembrane signaling..... These results provide clear experimental evidence that the N-cadherin-β-catenin signaling system participates in the analgesic effect of GDNF in neuropathic pain and help identify transmembrane and intracellular signal transduction mechanisms associated with GDNF's analgesic effects." [China] [This study is helping to define the mechanism of pain and pain relief, and may offer new ideas on ways to ease pain. DJS]

Panelli MC. 2017. JTM advances in uncharted territories: diseases and disorders of unknown etiology. J Transl Med. 15(1):192. "We are delighted to announce a new section in the Journal of Translational Medicine, 'Illnesses of Unknown Etiology'. This section aims to provide a translational medicine forum for the publication of research on illnesses, multisystem diseases and syndromes of unknown etiology. Examples of these include Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Fibromyalgia Syndrome." Free Article

[Panevin TS, Bobkova AO, Karateev AE, et al. 2022. Endogenous estrogen deficiency and the development of chronic musculoskeletal pain: A review]. Ter Arkh. 2022 Jun 17;94(5):683-688. [Article in Russian] "Sexual dimorphism of chronic diseases is a phenomenon determined by differences in the hormonal status of men and women. In this regard, estrogens, which have a complex effect on the body, are of great interest. In particular, estrogens play an important role in the natural control of pain and inflammation. A decrease in estrogen levels associated with menopause or iatrogenic effects (hysterectomy, use of aromotase inhibitors), as well as mutations of genes responsible for the synthesis of structural components of membrane estrogen receptors (ESR1 and ESR2), can significantly reduce the positive effects of these hormones. Deficiency of estrogen can become one of the reasons for the development of serious pathological changes in particular, the formation of chronic pain associated with the pathology of the musculoskeletal system."

Pang R, Wang S, Tian L et al. 2015. Complementary and integrative medicine at Mayo Clinic. Am J Chin Med. [Nov 30 Epub ahead of print.] "These results suggest that the diseases related to pain and psychological disorders are the main fields of CAM use. It also shows the increasing trend of the use of CAM at an academic medical center in the US." [Fibromyalgia was included in the group of illnesses studied.]

Pang, S. F., L. Li, E. A. Ayre, C. S. Pang, P. P. Lee, R. K. Xu, P. H. Chow, Z. H. Yu and S. Y. Shiu. 1998. Neuroendocrinology of melatonin in reproduction: recent developments. J Chem Neuroanat 14(3-4):157-66.

Pannemans J, Corsetti M. 2018. Opioid receptors in the GI tract: targets for treatment of both diarrhea and constipation in functional bowel disorders? Curr Opin Pharmacol. 43:53-58. "Opioids have been used for centuries, mostly as a sedative and to treat pain. Currently, they are used on a global scale for the treatment of acute and chronic pain in diseases as osteoarthritis, fibromyalgia, and low back pain. Binding of opioids on opioid receptors can cause a range of different effects such as changes in stress response, analgesia, motor activity and autonomic functions. This review provides a synthetic summary of the most recent literature on the use of drugs acting on mu-receptors to treat two prevalent functional bowel disorders, presenting with opposite bowel habit. Eluxadoline and naloxegol, methylnaltrexone and naldemedine are recently FDA and/or EMA approved drugs demonstrated to be effective and safe for treatment respectively of irritable bowel syndrome subtype diarrhea and opioid induced constipation."

Panton L, Simonavice E, Williams K et al. 2012. Effects of Class IV Laser Therapy on Fibromyalgia Impact and Function in Women with Fibromyalgia. J Altern Complement Med. [Nov 23 Epub ahead of print]. "This study provides evidence that LHT (laser heat therapy) may be a beneficial modality for women with FM in order to improve pain and upper body range of motion, ultimately reducing the impact of FM."

Panton LB, Kingsley JD, Toole T et al. 2006.  A comparison of physical functional performance and strength in women with fibromyalgia, age- and weight-matched controls, and older women who are healthy.  Phys Ther. 86(11):1479-1488.  “This study demonstrated that women with FM and older women who are healthy have similar lower-body strength and functionality, potentially enhancing the risk for premature age-associated disability.”

Paoletta M, Moretti A, Liguori S, et al. Efficacy and effectiveness of extracorporeal shockwave therapy in patients with myofascial pain or fibromyalgia: A scoping review. Medicina (Kaunas). 2022 Jul 28;58(8):1014. "Myofascial pain syndrome (MPS) and fibromyalgia (FM) are underestimated painful musculoskeletal conditions that could impact function and quality of life….Qualitative analysis suggests a beneficial role of ESWT for improving clinical and functional outcomes in people with MPS, whereas no evidence was found for FM." Free article (Italy) [Research indicates that chronic myofascial pain and dysfunction is musculoskeletal, and that fibromyalgia is central nervous system in nature. It is logical that a treatment with musculoskeletal effects will better target a musculoskeletal condition. DJS]

Papalambros NA, Santostasi G, Malkani RG et al. Acoustic enhancement of sleep slow oscillations and concomitant memory improvement in older adults. Front Hum Neurosci. 11:109. "Acoustic stimulation methods applied during sleep in young adults can increase slow wave activity (SWA) and improve sleep-dependent memory retention. It is unknown whether this approach enhances SWA and memory in older adults, who generally have reduced SWA compared to younger adults. Additionally, older adults are at risk for age-related cognitive impairment and therefore may benefit from non-invasive interventions. The aim of this study was to determine if acoustic stimulation can increase SWA and improve declarative memory in healthy older adults… Pulses of pink noise were delivered when the upstate of the slow wave was predicted. Each interval of five pulses ("ON interval") was followed by a pause of approximately equal length ("OFF interval"). …Verbal paired-associate memory was tested before and after sleep. Overnight improvement in word recall was significantly greater with acoustic stimulation compared to sham and was correlated with changes in SWA between ON and OFF intervals. Using the phase-locked-loop method to precisely target acoustic stimulation to the upstate of sleep slow oscillations, we were able to enhance SWA and improve sleep-dependent memory storage in older adults, which strengthens the theoretical link between sleep and age-related memory integrity." Free Article

Papazisis G, Tzachanis D. 2014. Pregabalin's abuse potential: a mini review focusing on the pharmacological profile. Int J Clin Pharmacol Ther. [May 21 Epub ahead of print.] "Pregabalin is approved for the treatment of partial epilepsy; generalized anxiety disorder; peripheral and central neuropathic pain and fibromyalgia. Its prescribing is rapidly increasing and total sales of the drug worldwide reached 4.6 billion US$ in 2012. Since entering widespread clinical use, reports of pregabalin abuse appeared more often, usually involving individuals with a history of abuse of other medications. The purpose of this mini review is to present available published data signaling pregabalin's abuse liability reflecting on the pharmacological characteristics that might enable this agent to trigger addictive behaviors."

Pappagallo, M. and L. J. Heinberg. 1997. Ethical issues in the management of chronic nonmalignant pain. Semin Neurol 17(3):203-211.

Pappagallo, M. 1998. Aggressive pharmacologic treatment of pain. Rheum Dis Clin North Am25(1):193-213, vii.

Pappolla MA, Manchikanti L, Andersen CR et al. 2019. Is insulin resistance the cause of fibromyalgia? A preliminary report. PLoS One. May 6;14(5):e0216079. "We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre- and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder." [Insulin resistance is a common perpetuating factor for both FM and chronic myofascial pain and dysfunction. There is a significant difference between "cause" and "perpetuating factor". DJS]

Paredes S, Cantillo S, Candido KD et al. An association of serotonin with pain disorders and its modulation by estrogens. Int J Mol Sci. 2019 Nov 15;20(22). [USA] "Ovarian hormones play an important role in pain perception, and are responsible, at least in part, for the pain threshold differences between the sexes....One of the most studied neurotransmitters related to pain disorders is serotonin. Estrogen can modify serotonin synthesis and metabolism, promoting a general increase in its tonic effects. Studies evaluating the relationship between serotonin and disorders such as irritable bowel syndrome, fibromyalgia, migraine, and other types of headache suggest a clear impact of this neurotransmitter, thereby increasing the interest in serotonin as a possible future therapeutic target." [Hormone imbalance can be an important part of pain control for any age or gender. DJS]

Park AJ, Paraiso MF. 2009.  Successful use of botulinum toxin type A in the treatment of refractory postoperative dyspareunia.  Obstet Gynecol. 114(2 Pt 2):484-487.  “Refractory dyspareunia presents a challenging therapeutic dilemma.  Case: A woman with defecatory dysfunction and dysparenuria presented with stage 2 prolapse.  She underwent laparoscopic and vaginal pelvic floor reconstruction with excision of endometriosis.  The patient experienced increased dysparenuria and de novo vaginismus postoperatively that were refractory to trigger point injections, physical therapy, and medical and surgical management.  She underwent botulinum toxin type A injections into her levator ani muscles, which allowed her to have sexual intercourse again after 2 years of apareunia with no recurrence of pain for 12 months.  Conclusion: Injecting botulinum toxin into the levator ani muscles shows promise for postoperative patients who develop vaginismus and do not respond to conservative therapy.”  [Men and women with sexual dysfunction must be assessed for myofascial TrPs in the pelvic floor, including perineum, plus low abdominal wall and rectal and vaginal TrPs.   There is so much unnecessary misery (and cost) due to lack of training on the part of practitioners. DJS] 

Park AJ, Paraiso MF. 2009.  Successful use of botulinum toxin type a in the treatment of refractory postoperative dyspareunia.  Obstet Gynecol. 114(2 Pt 2):484-487.  [This is one more indication of pain on intercourse caused by trigger points.  Perhaps much of this could be prevented by TrP injections of topical anesthetic along the surgical incision sites, as recommended in the myofascial texts.  DJS]

Park CH, Lee YW, Kim YC et al. 2012. Treatment experience of pulsed radiofrequency under ultrasound guided to the trapezius muscle at myofascial pain syndrome - a case report. Korean J Pain. 25(1):52-54. "Trigger point injection treatment is an effective and widely applied treatment for myofascial pain syndrome. The trapezius muscle frequently causes myofascial pain in neck area. We herein report a case in which direct pulsed radio frequency (RF) treatment was applied to the trapezius muscle. .... RF treatment produced continuous pain relief when the effective duration of trigger point injection was temporary in myofascial pain."

Park DJ, Kang JH, Yim YR et al. 2015. Exploring genetic susceptibility to fibromyalgia. Chonnam Med J. 51(2):58-65. "FM patients experience impaired quality of life and the disorder places a considerable economic burden on the medical care system. With the recognition of FM as a major health problem, many recent studies have evaluated the pathophysiology of FM. Although the etiology of FM remains unknown, it is thought to involve some combination of genetic susceptibility and environmental exposure that triggers further alterations in gene expression. Because FM shows marked familial aggregation, most previous research has focused on genetic predisposition to FM and has revealed associations between genetic factors and the development of FM, including specific gene polymorphisms involved in the serotonergic, dopaminergic, and catecholaminergic pathways. Free PMC Article

Park DJ, Takahashi Y, Kang JH et al. 2017. Anti-N-methyl-D-aspartate receptor antibodies are associated with fibromyalgia in patients with systemic lupus erythematosus: a case-control study. Clin Exp Rheumatol. [Mar 10 Epub ahead of print.] "The high concordance between systemic lupus erythematosus (SLE) and fibromyalgia (FM) suggests common underlying mechanisms related to pain and distress in both patient groups. Increasing evidence indicates that N-methyl-D-aspartate receptors (NMDARs) play a major role in the induction and maintenance of central sensitisation with chronic pain. In this study, we evaluated the role of anti-NMDAR antibodies in the development of FM in patients with SLE…. Multivariate analysis showed that the anti-GluN2B antibody was an independent predictor of concomitant FM and NPSLE…. To our knowledge, this report is the first to suggest that anti-NMDAR antibodies are associated with the pathogenesis of FM with SLE."

Park HJ, Moon DE. 2010. Pharmacologic management of chronic pain. Korean J Pain. 23(2):99-108. "This article provides a mechanism- and evidence-based approach to improve the outcome for pharmacologic management of chronic pain. The usual approach to treat mild to moderate pain is to start with a nonopioid analgesic. If this is inadequate, and if there is an element of sleep deprivation, then it is reasonable to add an antidepressant with analgesic qualities. If there is a component of neuropathic pain or fibromyalgia, then a trial with one of the gabapentinoids is appropriate. If these steps are inadequate, then an opioid analgesic may be added. For moderate to severe pain, one would initiate an earlier trial of a long term opioid. Skeletal muscle relaxants and topicals may also be appropriate as single agents or in combination. Meanwhile, the steps of pharmacologic treatments for neuropathic pain include (1) certain antidepressants (tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors), calcium channel alpha(2)-delta ligands (gabapentin and pregabalin) and topical lidocaine, (2) opioid analgesics and tramadol (for first-line use in selected clinical circumstances) and (3) certain other antidepressant and antiepileptic medications (topical capsaicin, mexiletine, and N-methyl-d-aspartate receptor antagonists). It is essential to have a thorough understanding about the different pain mechanisms of chronic pain and evidence-based multi-mechanistic treatment. It is also essential to increase the individualization of treatment."

Park KD, Lee WY, Park MH et al. 2018. High- versus low-energy extracorporeal shock-wave therapy for myofascial pain syndrome of upper trapezius: A prospective randomized single blinded pilot study. Medicine (Baltimore). 97(28):e11432. "To compare the efficacy of high- and low-energy extracorporeal shock wave therapy (ESWT) for patients with myofascial pain syndrome (MPS) of the upper trapezius..... High-energy ESWT was more effective in improving NDI and neck flexion ROM compared to the low-energy ESWT, suggesting superiority in functional improvement. Further studies are required to specify the effect of ESWT by energy intensity."

Park M, Zhang Y, Price LL et al. Mindfulness is associated with sleep quality among patients with fibromyalgia. Int J Rheum Dis. 2019 Nov 27. [Epub ahead of print] These authors looked at baseline data from a randomized trial. Their conclusion: "Higher mindfulness is associated with better sleep in patients with fibromyalgia, with pain interference, depression, and anxiety mediating this relationship", and further direct studies are warranted on this relationship.

Park SC, Kim KH. 2012. Effect of adding cervical facet joint injections in a multimodal treatment program for long-standing cervical myofascial pain syndrome with referral pain patterns of cervical facet joint syndrome. J Anesth. [May 31 Epub ahead of print]. Addition of therapeutic CFJ (cervical facet joint) injections to a multimodal treatment program is a useful therapeutic modality for patients, especially young patients, suffering from long-standing MPS with referral pain of CFJ syndrome.

Park SH, Baker AK, Krishna V, et al. Altered resting-state functional connectivity within corticostriatal and subcortical-striatal circuits in chronic pain. Sci Rep. 2022 Jul 25;12(1):12683. "Brain corticostriatal circuits are important for understanding chronic pain and highly relevant to motivation and cognitive processes. It has been demonstrated that in patients with chronic back pain, altered nucleus accumbens (NAcc)-medial prefrontal cortex (MPFC) circuit fMRI-based activity is predictive of patient outcome…. Together, expanding upon prior observed alterations in brain corticostriatal circuits, our results provide novel evidence of altered corticostriatal and mesolimbic circuits in chronic pain."

Parkitny L, Younger J. 2017. Reduced pro-inflammatory cytokines after eight weeks of Low-Dose Naltrexone for fibromyalgia. Biomedicines. 18;5(2). "In this 10-week, single-blind, crossover trial we tested the immune effects of eight weeks of oral administration of low-dose naltrexone (LDN). We enrolled eight women with an average age of 46 years, symptom severity of 62 out of 100, and symptom duration of 14 years. We found that LDN was associated with reduced plasma concentrations of interleukin (IL)-1β, IL-1Ra, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-15, IL-17A, IL-27, interferon (IFN)-α, transforming growth factor (TGF)-α, TGF-β, tumor necrosis factor (TNF)-α, and granulocyte-colony stimulating factor (G-CSF). We also found a 15% reduction of FM-associated pain and an 18% reduction in overall symptoms. The findings of this pilot trial suggest that LDN treatment in fibromyalgia is associated with a reduction of several key pro-inflammatory cytokines and symptoms.... The three main limitations of this study were the small sample size, the absence of a control group, and the short duration..... In particular, we do not how well the findings of our LDN studies translate to men. Second, because we did not use a control group, we cannot conclusively conclude that LDN was solely responsible for the magnitude of the immune change observed in this study. Finally, the short length of the study also meant that we may not have observed the maximal effects of LDN, as previous reports suggest that clinically-beneficial responses develop over months....We also recognize that some of the cytokines that significantly changed over the course of the study were not expressed by all individuals."

Parr, T. 1996.  Insulin exposure controls the rate of mammalian aging.  Mech Ageing Dev 88(1-2):75-82.

Parrott, Tom. 1999.  Using opioid analgesics to manage chronic noncancer pain in primary care.  J Am Board Fam Pract 12:293-306.

Parsons B, Argoff CE, Clair A et al. 2016. Improvement in pain severity category in clinical trials of pregabalin. J Pain Res. 9:779-785. "Compared with placebo, pregabalin is more often associated with clinically meaningful improvements in pain category in patients with FM (fibromyalgia), DPN (diabetic peripheral neuropathy), PHN (postherpetic neuralgia), or SCI neuropathic pain due to spinal cord injury." Patients with other conditions (including FM) did not significantly improve. (Pfizer study.) Free Article

Parvez S, Fatima G, Mahdi F. Unraveling the clinic-genetic association of catechol-o-methyltrasferase-rs4680g: A gene polymorphism in women with fibromyalgia syndrome. Wiad Lek. 2022;75(10):2439-2444. "Conclusions: AA genotype and A allele of the COMT rs4680 SNP were significantly associated with severity in FMS patients and also plays a significant role in the clinical manifestation of this disease."

Pascarelli, E. F. and J. J. Kella. 1993.  Soft-tissue injuries related to the use of the computer keyboard.  A clinical study of 53 severely injured persons.  J Occup Med 35(5):522-532.

Pasin T, Dogruoz Karatekin B, Pasin O. Pain, anxiety, and quality of life of COVID-19 survivors with myofascial pain syndrome: A cross sectional study. Pain Manag Nurs. 2023 Aug;24(4):400-405. "After recovering from COVID-19, patients with MPS showed increased pain, anxiety, disability, and decreased quality of life."

Pasisson TS, Graven-Neilsen T. 2012. Experimental pelvic pain facilitates pain provocation tests and causes regional hyperalgesia. Pain. 153(11):2233-2240. This study showed that an extra-articular sacroiliac joint structure (the long posterior sacroiliac ligament) can hold pain receptors that can cause referred pain and regional hyperalgesia that is sensitive to manual pain provocation testing.

Pasquali R, Vicennati V. 2000.  The abdominal obesity phenotype and insulin resistance are associated with abnormalities of the hypothalamic-pituitary-adrenal axis in humans.  Horm Metab Res 32(11-12):521-525.

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Passard A, Attal N, Benadhira R et al. 2007.  Effects of unilateral repetitive transcranial magnetic stimulation of the motor cortex on chronic widespread pain in fibromyalgia.  Brain. 130(Pt 10):2661-2670.  “…unilateral rTMS of the motor cortex induces a long-lasting decrease in chronic widespread pain and may therefore constitute an effective alternative analgesic treatment for fibromyalgia.”

Passik SD, Kirsh KL, Whitcomb L et al. 2004.  A new tool to assess and document pain outcomes in chronic pain patients receiving opioid therapy.  Clin Ther 26(4):552-561.  “In this study, the PADT appeared to be a useful tool for clinicians to guide the evaluation of several important outcomes during opioid therapy and provide a simple means of documenting patient care.”

Pastore EA, Katzman WB. 2012. Recognizing Myofascial Pelvic Pain in the Female Patient with Chronic Pelvic Pain. J Obstet Gynecol Neonatal Nurs. 41(5):680-691. "Myofascial pelvic pain (MFPP) is a major component of chronic pelvic pain (CPP) and often is not properly identified by health care providers. The hallmark diagnostic indicator of MFPP is myofascial trigger points in the pelvic floor musculature that refer pain to adjacent sites. Effective treatments are available to reduce MFPP, including myofascial trigger point release, biofeedback, and electrical stimulation. An interdisciplinary team is essential for identifying and successfully treating MFPP."

Patel J, Saba Javed S. 2021. Myofascial pain syndrome and SARS-CoV-2: a case series. Pain Manag. Oct 4; Online ahead of print. Chart reviews were performed and demonstrated patients who had a history of chronic pain had subsequent episodes of worsening exacerbations of pain, more specifically trigger points, after being diagnosed with coronavirus. MFPS and SARS-CoV-2 are proposed to be correlated amongst chronic pain patients. Potential pathological mechanisms include coronavirus-induced hypoxic muscle dysfunctions as well as psychological stress triggering pain receptors, leading to myofascial pain syndrome.

Patel M, Aiello M. Successful treatment of acute worsening complex regional pain syndrome in affected dominant right-hand from secondary pathology of new onset third and fourth digit trigger finger. Case Reports Plast Surg Hand Surg. 2022 Apr 27;9(1):123-125. "65 year old male with preexisting Complex Regional Pain Syndrome (CRPS) in right dominant hand with sudden onset of right third and fourth digit trigger finger successfully treated with flexor tendon sheath corticosteroid and lidocaine injection resulting in long-term resolution of symptoms without causing widely believed aggravation of CRPS." Free article

Patel N, Patel M, Poustinchian B. 2019. Dry needling-induced pneumothorax. J Am Osteopath Assoc.; 119(1):59-62. "Some of the complications secondary to this procedure include cardiac tamponade, hematoma, infection, nerve injury, and pneumothorax. Although the incidence is low, the complications can be potentially life threatening. We present the case of a 44-year-old man who had dry needling of the infraspinatus, supraspinatus, rhomboid, and paraspinal muscles with subsequent development of a left apical pneumothorax. Given that the pneumothorax was small, the patient had good recovery with supplemental oxygen. Although the incidence of pneumothorax is very low, it is an important diagnosis to consider for a patient presenting with dry cough, malaise, chest pain, or shortness of breath after a dry needling procedure. Patients should be made aware of these potential complications as part of an informed consent."

Patel VB, Wasserman R, Imani F. 2015. Interventional therapies for chronic low back pain: A focused review (efficacy and outcomes). Anesth Pain Med. 5(4):e29716. "Lower back pain is considered to be one of the most common complaints that brings a patient to a pain specialist. Several modalities in interventional pain management are known to be helpful to a patient with chronic low back pain. Proper diagnosis is required for appropriate intervention to provide optimal benefits. From simple trigger point injections for muscular pain to a highly complex intervention such as a spinal cord stimulator are very effective if chosen properly. Lower back pain is a major healthcare issue and this review article will help educate the pain practitioners about the current evidence based treatment options." Free PMC Article

Patil S, Daniel G, Tailor Y, et al. 2022. Bladder pain syndrome/interstitial cystitis response to nerve blocks and trigger point injections. BJUI Compass. 2022 Jun 18;3(6):450-457. "Bladder pain syndrome (BPS)/interstitial cystitis (IC) is a debilitating condition characterised by bladder/pelvic pain and pressure as well as persistent or recurrent urinary symptoms in the absence of an identifiable cause. It is hypothesised that in addition to organ specific visceral hypersensitivity, contributions of the hypertonic pelvic floor, peripheral sensitisation, and central sensitisation exacerbate this condition... Analysis suggests the treatment was effective at ameliorating bladder pain and function including urinary urgency, frequency, and burning in BPS/IC patients."

Patru S, Padureanu R, Dumitrescu F et al. 2021. Influence of multidisciplinary therapeutic approach on fibromyalgia patients. Exp Ther Med. May;21(5):528. "In order to control and improve most of the FM symptoms, besides proper medication, we suggest an interdisciplinary intervention mainly focusing on long-term individualized kinetic therapy. The simultaneous integration of a cognitive-behavioural and occupational therapy intervention could be the element that completes the complex treatment of FM patients."

Patten DK, Schultz BG, Berlau DJ. 2018. The safety and efficacy of low-dose naltrexone in the management of chronic pain and inflammation in multiple sclerosis, fibromyalgia, Crohn's disease, and other chronic pain disorders. Pharmacotherapy. 38(3):382-389. "Low-dose naltrexone has been used off-label for treatment of pain and inflammation in multiple sclerosis, Crohn's disease, fibromyalgia, and other diseases. Naltrexone is a mu-opioid receptor antagonist indicated by the Food and Drug Administration for opioid and alcohol dependence. It is hypothesized that lower than standard doses of naltrexone inhibit cellular proliferation of T and B cells and block toll-like receptor 4, resulting in an analgesic and anti-inflammatory effect. It is the purpose of this review to examine the evidence of the safety, tolerability, and efficacy of low-dose naltrexone for use in chronic pain and inflammatory conditions. Currently, evidence supports the safety and tolerability of low-dose naltrexone in multiple sclerosis, fibromyalgia, and Crohn's disease. Fewer studies support the efficacy of low-dose naltrexone, with most of these focusing on subjective measures such as quality of life or self-reported pain. These studies do demonstrate that low-dose naltrexone has subjective benefits over placebo, but evidence for more objective measures is limited. However, further randomized controlled trials are needed to determine the efficacy of low-dose naltrexone due to insufficient evidence supporting its use in these disease states. This review provides practitioners with the extent of low-dose naltrexone evidence so that they can be cognizant of situations where it may not be the most appropriate therapy."

Paul TM , Hoo JS, Chae J et al. 2012. Central Hypersensitivity in Patients with Subacromial Impingement Syndrome. Arch Phys Med Rehabil. [Jul 9 Epub ahead of print]. "This study provides further evidence that SIS (secondary hyperalgesia) patients have significantly lower PPTs (pain-pressure thresholds) than controls in both local and distal areas from their affected arm consistent with primary and secondary hyperalgesia, respectively. Data suggest the presence of central sensitization among subjects with chronic SIS."

Paulin J, Andersson L, Nordin S. 2016. Characteristics of hyperacusis in the general population. Noise Health. 18(83):178-184. "High age, female sex, and high education were associated with hyperacusis, and that trying to avoid sound sources, being able to affect the sound environment, and having sought medical attention were common reactions and behaviors. Posttraumatic stress disorder, chronic fatigue syndrome, generalized anxiety disorder, depression, exhaustion, fibromyalgia, irritable bowel syndrome, migraine, hearing impairment, tinnitus, and back/joint/muscle disorders were comorbid with hyperacusis. The results provide ground for future study of these characteristic features being risk factors for development of hyperacusis and/or consequences of hyperacusis".

Paulson, M., A. Norberg, E. Danielson. 2002. Men living with fibromyalgia-type pain: experiences as patients in the Swedish health care system. J Adv Nurs 40(1):87-95. Men with chronic diffuse pain waited a long time to be referred to a specialty clinic.  If the staff was interested and well-trained, the men experienced well-being in spite of the recognition that there was no cure. Lack of respect from the staff caused the patients to feel neglected, even if they had otherwise adequate care.

Pavan PG, Stecco A, Stern R et al. 2014. Painful connections: densification versus fibrosis of fascia. Curr Pain Headache Rep. 18(8):441. "Deep fascia has long been considered a source of pain, secondary to nerve pain receptors becoming enmeshed within the pathological changes to which fascia are subject. Densification and fibrosis are among such changes. They can modify the mechanical properties of deep fasciae and damage the function of underlying muscles or organs. Distinguishing between these two different changes in fascia, and understanding the connective tissue matrix within fascia, together with the mechanical forces involved, will make it possible to assign more specific treatment modalities to relieve chronic pain syndromes. This review provides an overall description of deep fasciae and the mechanical properties in order to identify the various alterations that can lead to pain. Diet, exercise, and overuse syndromes are able to modify the viscosity of loose connective tissue within fascia, causing densification, an alteration that is easily reversible. Trauma, surgery, diabetes, and aging alter the fibrous layers of fasciae, leading to fascial fibrosis."

Pawlukiewicz M, Kochan M, Niewiadomy P, et al. Fascial Manipulation Method Is Effective in the Treatment of Myofascial Pain, but the Treatment Protocol Matters: A Randomised Control Trial-Preliminary Report. J Clin Med. 2022 Aug 4;11(15):4546. "There are many therapeutic methods targeting fascia. However, the only method whose basic assumption is to eliminate the densification of fascia is Fascial Manipulation….The patients were divided into four groups subjected to different treatment protocols: group 1-underwent the standard FM treatment protocol (STP), group 2-modified protocol (MTP), group 3-modified protocol 2 (MTP2), and the control group (CG)-did not undergo any therapy. Each protocol involved three treatments at intervals of 7-10 days and a follow-up examination after 30 days. The outcome was pain level measured using the VAS…. Only the CG group did not display significant changes…. FM-based therapy results in pain relief. However, there are differences in the dynamics and durability of the results depending on the chosen protocol." Free article (Poland) [In this case, FM indicates Fascial Manipulation©, a specific fascial therapy. DJS]

Paxton SE. 2011. Perioperative care of the patient with fibromyalgia. AORN J. 93(3):380-389.

Payne LA, Seidman LC, Sim MS et al. 2019. Experimental evaluation of central pain processes in young women with primary dysmenorrhea. Pain. [Jan 31 Epub ahead of print] "Results indicated enhanced pain sensitivity in girls with PD as measured by heat pain tolerance and threshold, compared to healthy controls. These group differences were evident at all phases of the menstrual cycle. No group differences in cold pain tolerance, temporal summation, or conditioned pain modulation were evident at any phase of the menstrual cycle. These data suggest some evidence of central sensitization in girls with PD, although no evidence of deficient pain modulation was observed. Future research should focus on identifying other potential phenotypes for PD to identify those at risk for developing other pain problems."

Payne P, Crane-Godreau MA. 2012. Meditative movement for depression and anxiety. Front Psychiatry. 4:71. This review from Dartmouth "…focuses on Meditative Movement (MM) and its effects on anxiety, depression, and other affective states. MM is a term identifying forms of exercise that use movement in conjunction with meditative attention to body sensations, including proprioception, interoception, and kinesthesis. MM includes the traditional Chinese methods of Qigong (Chi Kung) and Taijiquan (Tai Chi), some forms of Yoga, and other Asian practices, as well as Western Somatic practices; however this review focuses primarily on Qigong and Taijiquan…. Results suggest that MM may be at least as effective as conventional exercise or other interventions in ameliorating anxiety and depression; however, study quality is generally poor and there are many confounding factors. This makes it difficult to draw definitive conclusions at this time. We suggest, however, that more research is warranted, and we offer specific suggestions for ensuring high-quality and productive future studies."

Payne RJ, Kost KM, Frenkiel S, et al. 2006.  Otolaryngeal inflammation assessed using the reflux finding score in obstructive sleep apnea. 134(5):836-842.  Laryngeal inflammation is prevalent among OSA patients and correlates with laryngeal sensory dysfunction, attenuation of the LAR (laryngeal adductor reflex), and apnea severity.  [GERD may activate laryngeal TrPs. DJS]

Pearl C, Moxley B, Perry A, et al. Successful treatment of myofascial pain syndrome (MPS) with surgical cauterization of temporalis muscle trigger points: A case report. Dent J (Basel). 2022 Dec 23;11(1):3 "This technique involves identifying and marking the patient's trigger points and surgically cauterizing each location using a Bovie electrosurgical unit. While traditional trigger point injection therapy for myofascial pain syndrome is a well-described technique with acceptable pain relief expected for a period of 8-12 weeks, this technique provided up to 24 months of adequate pain relief in a patient."

Peckham AM, Evoy KE, Ochs L et al. 2018. Gabapentin for Off-Label Use: Evidence-Based or Cause for Concern? Subst Abuse. Sep 23;12:1178221818801311. "Gabapentin is widely used in the United States for a number of off-label indications, often as an alternative to opioid therapy. Increasing evidence has emerged suggesting that gabapentin may not be as benign as once thought and may be associated with substance abuse in concert with opioids. With concerns for safety mounting, it is prudent to examine the efficacy of gabapentin across its many uses to understand the risk-benefit balance. Reviews on off-label indications such as migraine, fibromyalgia, mental illness, and substance dependence have found modest to no effect on relevant clinical outcomes. This high-quality evidence has often been overshadowed by uncontrolled studies and limited case reports. Furthermore, the involvement of gabapentin in questionable marketing schemes further calls its use into question. Overall, clinicians should exercise rigorous appraisal of the available evidence for a given indication, and researchers should conduct larger, higher-quality studies to better assess the efficacy of gabapentin for many of its off-label uses."

Pecos-Martin D, Montanez-Aguilera FJ, Gallego-Izquierdo T et al. 2015. The effectiveness of dry needling on the lower trapezius in patients with mechanical neck pain: A randomized clinical trial. Arch Phys Med Rehabil. [Jan 9 Epub ahead of print.] "The application of dry needling into an active MTrP of the LT muscle induces significant changes in the VAS, NPQ and PPT levels compared to the application of dry needling in other locations of the same muscle in patients with mechanical neck pain."

Pednekar DD, Amin MR, Fekri Azgomi H et al. Characterization of cortisol dysregulation in fibromyalgia and chronic fatigue syndromes: A State-Space approach. IEEE Trans Biomed Eng. 2020 Mar 5. [Epub ahead of print] "Our results show that the clearance rate of cortisol is lower in FMS patients as compared to their matched healthy individuals based on a simplified cortisol secretion model. Moreover, the number, magnitude, and energy of hormonal secretory events are lower in FMS patients. During early morning hours, the magnitude and energy of the hormonal secretory events are higher in CFS patients…. Due to lower cortisol clearance rate, there is a higher accumulation of cortisol in FMS patients as compared to their matched healthy subjects. As the FMS patient accumulates higher cortisol residues, internal inhibitory feedback regulates the hormonal secretory events. Therefore, the FMS patients show a lower number, magnitude, and energy of hormonal secretory events. Though CFS patients have the same number of secretory events, they secrete lower quantities during early morning hours."

Pedrelli A, Stecco C, Day JA. 2009. treating patellar tendinopathy with fascial manipulation. J Bodyw Mov Ther 13(1):73-80. Trigger points in quadriceps muscles can cause kneecap pain with motor incoordination. Fascial manipulation technique of the quadriceps may relieve kneecap pain and dysfunction, and thus the focus of therapy may need to be the anterior thigh.

Pedretti, Lorraine Williams, ed. April 1996. Occupational Therapy: Practice Skills for PhysicalDisfunction. Mosby-Year Book. Chap. 21. Pope-Davis, S. A.

Pelaez I, Ferrera D, Barjola P et al. 2019. Subliminal emotional pictures are capable of modulating early cerebral responses to pain in fibromyalgia. PLoS One. 14(6):e0217909. "Our findings show an early cerebral modulation of pain…in FM patients, suggesting that only pain-related information, even when it is unconsciously perceived, is capable to enhance exogenous (automatic) attention, increasing the neural activity involved in processing painful stimulation. Further research is needed to fully understand unconscious emotional influences on pain in fibromyalgia."

Pena VN, Engel N, Gabrielson AT, et al. 2021. Diagnostic and management strategies for patients with chronic prostatitis and chronic pelvic pain syndrome. Drugs Aging. Oct;38(10):845-886. "The best studied pharmacologic therapies include antibiotics, alpha-blockers, anti-inflammatory and immunomodulatory agents, phytotherapies, phosphodiesterase inhibitors, hormonal agents, neuromodulatory agents, and antidepressants. The best studied non-pharmacological therapies include pelvic floor physical therapy, myofascial trigger point release, acupuncture and electroacupuncture, psychological support and biofeedback, and electrocorporeal shockwave therapy and local thermotherapy."

Peng PW. 2012. Tai Chi and Chronic Pain. Reg Anesth Pain Med. [May 17 Epub ahead of print]. Most tai chi studies were found to be of low quality. "Only 5 pain conditions were reviewed: osteoarthritis, fibromyalgia, rheumatoid arthritis, low back pain, and headache. Of these, Tai Chi seems to be an effective intervention in osteoarthritis, low back pain, and fibromyalgia."

Peng PW, Castano ED. 2005.  Survey of chronic pain practice by anesthesiologists in Canada.  Can J Anaesth. 52(4):383-389.  “While 38% of responding anesthesiologists were involved in CPP (chronic pain practice), in the majority of cases, this accounted for less than 20% of their clinical time.  Thirty percent of those involved in CPP had previous training in pain management.  The types of CPP included nerve blocks (84%) and pharmacological treatment (60%) in non-cancer pain (85%) and cancer pain (50%) patients.”  “Approximately one-third of anesthesiologists surveyed incorporate chronic pain in their practice and their pattern of practice is widely diversified.”  Only 30% of these anesthesiologists had previous training in chronic pain management.  Trigger point injections were responsible for 70% of this work.  [One must wonder how many of the patients had proper placement and range of motion stretching for their injections, and how much was done to identify and control the perpetuating factors–both minimal and necessary parts of proper treatment of TrPs. DJS]

Peng Z, Xu N, Bian Z et al. 2017. [Discussion on "dry needling" being part of acupuncture]. Zhongguo Zhen Jiu. 37(6):663-667. [Article in Chinese] "We think that all the methods of puncturing into the skin to prevent and treat diseases are belong to acupuncture science. In spite of its basic theory of meridian and acupoint, anatomy and physiology have been important parts of modern acupuncture science. "Dry needling", however, is limited to trigger point theory. As for the positions, acupuncture is applied mainly at acupoints, involving in skin, muscles, tendons, vessels and nerves; while "dry needling" is used mostly at muscles. The needles of acupuncture are in various lengths and diameters and its manipulations are abundant, including the traditional skills and the achievements of modern science and technology research, such as electroacupuncture. It is different from the "dry needling" with the single tool and manipulation. Thus, acupuncture is suitable for a large range of syndromes, but "dry needling" is mainly for fascia muscularis pain and other related disorders. The acupuncturists need to embrace Chinese and western medicine, which is more rigorous than the training for "dry needling" practitioners. Based on the above reasons, we consider "dry needling" as part of acupuncture science, and it is a method during the modern development of traditional acupuncture. [I respectfully disagree with these authors. Neurosurgery training may be more "rigorous" than dental school, but I would not go to a neurosurgeon to maintain my dental health. The skill set is different. Trigger point training is specific to trigger points, and a medical degree in other disciplines do not automatically confer the specific training in trigger point referral patterns and symptoms, palpation, positioning, and needling techniques. The only similarities are the use of the acupuncture needles. I believe that acupuncturists and other doctors should be required to master specific relevant trigger point training before they are allowed to practice dry needling or trigger point injection. We do need standardizing for training in these myofascial medicine procedures. DJS]

Penn IW, Chuang E, Chuang TY et al. 2019. Bidirectional association between migraine and fibromyalgia: retrospective cohort analyses of two populations. BMJ Open. Apr 8;9(4):e026581. "Fibromyalgia (FM) and migraine are common pain disorders that tend to coexist. This study determined whether these two conditions exhibited any mutual influences.... The present study revealed a bidirectional link between FM and migraine."

Penny HA, Aziz , Ferrar M et al. 2016. Is there a relationship between gluten sensitivity and postural tachycardia syndrome? Eur J Gastroenterol Hepatol. 28(12):1383-1387. "This is the first study to suggest a potential association between gluten-related disorders and POTS. A prospective study evaluating this relationship further may enable a better understanding and management of these conditions."

Penrod JR, Bernatsky S, Adam V et al.  2004.  Health services costs and their determinants in women with fibromyalgia.  J Rheumatol. 31(7):1391-1398.  Women with FMS use a high level of both conventional and complementary medical services.  Although there are significant direct costs associated with FMS, 70% of the economic burden on the patient is indirect, and often unrecognized.

Perea G, Navarrete M, Araque A. 2009.  Tripartite synapses: astrocytes process and control synaptic information.  Trends Neurosci. 32(8):421-431.  This explanation of a three part synaptic system of information flow between pre- and post-synaptic neurons, astrocytes (glial cells) is elegant.  The astrocytes not only respond to synaptic transmission but regulate it.  [Astrocytes are the controllers of neural plasticity, including the central sensitization of FM. DJS]  Contrasting to the old view of neuron dominance of information exchange in the central nervous system, the emerging view indicates that the synaptic activity is a coordinated effort by both the glial and the neurons. 

Perea G, Araque A. 2005.  Glial calcium signaling and neuron-glia communication.  Cell Calcium [ Aug 13 Epub ahead of print]  “There is a new concept of the synaptic physiology - ‘the tripartite synapse’, where astrocytes exchange information with the pre- and post-synaptic elements and participate as dynamic regulatory elements in neurotransmission.  The control of the Ca(2+) excitability in astrocytes is a key element in this loop of information exchange.  The ability of astrocytes to respond to neuronal activity and discriminate between the activity of different synapses, the modulation of the astrocytic cellular excitability by the synaptic activity, and the expression of cellular intrinsic properties indicate that astrocytes are endowed with cellular computational characteristics that process synaptic information.”

Pereira MP, Kremer AE, Mettang T et al. 2016. Chronic pruritus in the absence of skin disease: Pathophysiology, diagnosis and treatment. Am J Clin Dermatol. [May 23 Epub ahead of print.] "Chronic pruritus arises not only from dermatoses, but also, in up to half of cases, from extracutaneous origins. A multitude of systemic, neurological, psychiatric, and somatoform conditions are associated with pruritus in the absence of skin disease. Moreover, pruritus is a frequently observed side effect of many drugs. It is therefore difficult for physicians to make a correct diagnosis. Chronic pruritus patients frequently present to the dermatologist with skin lesions secondary to a long-lasting scratching behavior, such as lichenification and prurigo nodularis. A structured clinical history and physical examination are essential in order to evaluate the pruritus, along with systematic, medical history-adapted laboratory and radiological tests carried out according to the differential diagnosis. For therapeutic reasons, a symptomatic therapy should be promptly initiated parallel to the diagnostic procedures. Once the underlying factor(s) leading to the pruritus are identified, a targeted therapy should be implemented. Importantly, the treatment of accompanying disorders such as sleep disturbances or mental symptoms should be taken into consideration. Even after successful treatment of the underlying cause, pruritus may persist, likely due to chronicity processes including peripheral and central sensitization or impaired inhibition at spinal level. A vast arsenal of topical and systemic agents targeting these pathophysiological mechanisms has been used to deter further chronicity. The therapeutic options currently available are, however, still insufficient for many patients."

Peres M, Zukerman E, Senne Soares et al. 2004. Cerebrospinal fluid glutamate levels in chronic migraine.  Cephalalgia 24(9):735-739.  This study indicates that patients with both FMS and migraines may have a more severe central sensitization process than patients with FMS who do not have migraines.  The headache intensity of the chronic migraine patients correlated with cerebrospinal glutamate levels.

Perez-Cabezas V, Ruiz-Molinero C, Jimenez-Rejano JJ et al. Effectiveness of an eye-cervical re-education program in chronic neck pain: A randomized clinical trial. Evid Based Complement Alternat Med. 2020 Feb 26;2020:2760413. "Eye-Cervical Re-education Program is effective at relieving pain pressure thresholds in the upper trapezius, right levator scapula, and left splenius capitis and especially effective for increasing the cervical range of motion." [This paper includes the exercises that were used in the trial. DJS]

Perez de Heredia-Torres M, Huertas-Hoyas E, Maximo-Bocanegra N et al. 2016. Cognitive performance in women with fibromyalgia: A case-control study. Aust Occup Ther J. [Apr 5 Epub ahead of print.] "Women with fibromyalgia exhibited a decreased cognitive ability compared to healthy controls, which negatively affected the performance of daily activities, such as upper limb dressing, feeding and personal hygiene. Patients required more time to perform activities requiring both attention and perception, decreasing their functional independence. Also, they displayed greater errors when performing activities requiring the use of memory….Occupational therapists treating women with fibromyalgia should consider the negative impact of possible cognitive deficits on the performance of daily activities and offer targeted support strategies.

Perez-Palomares S, Olivan-Blazquez B, Magallon-Botaya R et al. 2010. Percutaneous electrical nerve stimulation versus dry needling: effectiveness in the treatment of chronic low back pain. J Musculoskel Pain. 18(1). “At least one TrP was found in all patients, most commonly situated in the quadratus lumborum muscle [97.6 percent]. The improvement achieved for both treatment groups was similar in all the measured variables, although the DN (dry needling) group carried out fewer sessions than the PENS (percutaneous electrical nerve stimulation) group.”  [The term “chronic low back pain” is a description, not a diagnosis, and our reimbursement system must be set up to reflect this.  Quadratus lumborum TrPs are potentially disabling and can cause tremendous amount of pain and dysfunction, and must be part of the assessment for causes of chronic low back pain.  DJS]

Perez-Palomares S, Olivan-Blazquez B, Perez-Palomares A et al. 2017. Contribution of dry needling to individualized physical therapy treatment of shoulder pain: A randomized clinical trial. J Orthop Sports Phys Ther. 47(1):11-20. "Dry needling did not offer benefits in addition to personalized, evidence based physical therapy treatment for patients with nonspecific shoulder pain."

Pergolizzi J, Ahlbeck K, Aldington D et al. 2013. The development of chronic pain: physiological CHANGE necessitates a multidisciplinary approach to treatment. Curr Med Res Opin. [Jul 3 Epub ahead of print]. "Chronic pain is currently under-diagnosed and under-treated, partly because doctors' training in pain management is often inadequate. This situation looks certain to become worse with the rapidly increasing elderly population unless there is a wider adoption of best pain management practice. This paper reviews current knowledge of the development of chronic pain and the multidisciplinary team approach to pain therapy. The individual topics covered include nociceptive and neuropathic pain, peripheral sensitization, central sensitization, the definition and diagnosis of chronic pain, the biopsychosocial model of pain and the multidisciplinary approach to pain management. This last section includes an example of the implementation of a multidisciplinary approach in Belgium and describes the various benefits it offers; for example, the early multidimensional diagnosis of chronic pain and rapid initiation of evidence-based therapy based on an individual treatment plan. The patient also receives continuity of care, while pain relief is accompanied by improvements in physical functioning, quality of life and emotional stress. Other benefits include decreases in catastrophizing, self-reported patient disability, and depression. Improved training in pain management is clearly needed, starting with the undergraduate medical curriculum, and this review is intended to encourage further study by those who manage patients with chronic pain."

Pergolizzi JV Jr, LeQuang JA, Berger GK et al. 2017. The basic pharmacology of opioids informs the opioid discourse about misuse and abuse: A review. Pain Ther. [Mar 24 Epub ahead of print.] "Morphine and other opioids are widely used to manage moderate to severe acute pain syndromes, such as pain associated with trauma or postoperative pain, and they have been used to manage chronic pain, even chronic nonmalignant pain. However, recent years have seen a renewed recognition of the potential for overuse, misuse, and abuse of opioids. Therefore, prescribing opioids is challenging for healthcare providers in that clinical effectiveness must be balanced against negative outcomes-with the possibility that neither are achieved perfectly. The current discourse about the dual 'epidemics' of under-treatment of legitimate pain and the over-prescription of opioids is clouded by inadequate or inaccurate understanding of opioid drugs and the endogenous pain pathways with which they interact. An understanding of the basic pharmacology of opioids helps inform the clinician and other stakeholders about these simultaneously under- and over-used agents."

Pergolizzi JV Jr, Raffa RB, Taylor R Jr. 2014. Treating Acute Pain in Light of the Chronification of Pain. Pain Manag Nurs. 15(1):380-390. "The progression of acute to chronic pain, also known as pain chronification, remains incompletely understood. Biologic factors involved in this transition include central sensitization, neuroplastic changes, altered pain modulation, and changes to the "neuromatrix." Chronic pain may involve irreversible pathophysiologic changes, so interrupting the cascade of events that allows acute pain to advance to chronic pain is of crucial importance. This involves recognition and prompt treatment of acute pain, better awareness and application of evidence-based guidelines on pain management by all clinicians (not just pain specialists), and patient education. By interrupting nociceptive input in acute pain conditions, it might be possible to prevent transition to chronic pain syndromes."

Perneger, T. V., P. K. Whelton and M. J. Klag. Risk of kidney failure associated with the use ofacetominophen, aspirin, and nonsteroidal anti-inflammatory drugs. N Engl J Med 331(25):1675-9.

Perreault T, Ball A, Dommerholt J et al. 2022. Intramuscular electrical stimulation to trigger points: insights into mechanisms and clinical applications-A scoping review. J Clin Med. 2022 Oct 13;11(20):6039. "Based on the results of the included studies, IMES within a TrP region was reported to normalize muscle blood flow, decrease endplate noise of the TrP and elicit antinociceptive effects, at least partially, through engaging supraspinal descending pain inhibitory systems. At present, no clinical implications can be determined on the use of IMES to TrPs due to the limited amount and quality of the available evidence."

Perreault T, Dunning J, Butts R. 2017. The local twitch response during trigger point dry needling: Is it necessary for successful outcomes? J Bodyw Mov Ther. 21(4):940-947. "Myofascial trigger point (MTrP) injection and trigger point dry needling (TrPDN) are widely accepted therapies for myofascial pain syndrome (MPS)….Several studies show that eliciting a LTR (local twitch response) does not correlate with changes in pain and disability, and multiple systematic reviews have failed to conclude whether the LTR is relevant to the outcome of TrPDN. Post needling soreness is consistently reported in studies using repeated in and out needling to elicit LTRs and increases in proportion to the number of needle insertions. In contrast, needle winding without LTRs to MTrPs and connective tissue is well supported in the literature, as it is linked to anti-nociception and factors related to tissue repair and remodeling. Additionally, the positive biochemical changes in the MTrP after needling may simply be a wash out effect related to local vasodilation. While the LTR during TrPDN appears unnecessary for managing myofascial pain and unrelated to many of the positive effects of TrPDN, further investigation is required."

Perrot S. 2015. Osteoarthritis pain Best Pract Res Clin Rheumatol. 29(1):90-7. "Osteoarthritis (OA) represents one of the most frequently occurring painful conditions. Pain is the major OA symptom, involving both peripheral and central neurological mechanisms. OA pain is initiated from free axonal endings located in the synovium, periosteum bone, and tendons, but not in the cartilage. The nociceptive message involves not only neuromediators and regulating factors such as neuronal growth factor (NGF) but also central modifications of pain pathways. OA pain is a mixed phenomenon where nociceptive and neuropathic mechanisms are involved in both the local and central levels. OA pain perception is influenced by multiple environmental, psychological, or constitutional factors, and OA pain intensity is not correlated with joint degradation. OA pain may present with different clinical features: constant and intermittent pain, with or without a neuropathic component, and with or without central sensitization. Finally, OA pain should be considered as a complex and not unique pain condition, where precise clinical assessment may drive specific therapeutic approaches."

Perrot S. 2012. If fibromyalgia did not exist, we should have invented it. A short history of a controversial syndrome. Reumatismo. 64(4):186-193. "Fibromyalgia is a recent disease, and some physicians remain doubtful about its reality. The history of fibromyalgia is a story of controversies: the fight between subjectivity and cartesianism, and between old mind and body concepts. Fibromyalgia represents the emblematic condition of unexplained medical symptoms, far from well-defined diseases with objective biomarkers. In this review we will follow the fibromyalgia story along the ages and sciences to better understand this complex pain disorder, between soma and psyche, and between medicine and psycho-sociology and to demonstrate that fibromyalgia exists; we have not invented it."

Perrot S, Choy E, Petersel D et al. 2012. Survey of physician experiences and perceptions about the diagnosis and treatment of fibromyalgia. BMC Health Serv Res. 12(1):356. "Fibromyalgia (FM) is a condition characterized by widespread pain and is estimated to affect 0.5-5% of the general population. Historically, it has been classified as a rheumatologic disorder, but patients consult physicians from a variety of specialties in seeking diagnosis and ultimately treatment. Patients report considerable delay in receiving a diagnosis after initial presentation, suggesting diagnosis and management of FM might be a challenge to physicians....A questionnaire survey of 1622 physicians in six European countries, Mexico and South Korea was conducted. Specialties surveyed included primary care physicians (PCPs; n=809) and equal numbers of rheumatologists, neurologists, psychiatrists and pain specialists. The sample included experienced doctors, with an expected clinical caseload for their specialty. Most (>80%) had seen a patient with FM in the last 2 years. Overall, 53% of physicians reported difficulty with diagnosing FM, 54% reported their training in FM was inadequate, and 32% considered themselves not knowledgeable about FM. Awareness of American College of Rheumatology classification criteria ranged from 32% for psychiatrists to 83% for rheumatologists. Sixty-four percent agreed patients found it difficult to communicate FM symptoms, and 79% said they needed to spend more time to identify FM. Thirty-eight percent were not confident in recognizing the symptoms of FM, and 48% were not confident in differentiating FM from conditions with similar symptoms. Thirty-seven percent were not confident developing an FM treatment plan, and 37% were not confident managing FM patients long-term. In general, rheumatologists reported least difficulties/greatest confidence, and PCPs and psychiatrists reported greatest difficulties/least confidence....Diagnosis and managing FM is challenging for physicians, especially PCPs and psychiatrists, but other specialties, including rheumatologists, also express difficulties. Improved training in FM and initiatives to improve patient-doctor communication are needed and may help the management of this condition. [This free article is available on the Internet, and confirms what many patients know all too well. DJS]

Perrot S, Russell IJ. 2014. More ubiquitous effects from non-pharmacologic than from pharmacologic treatments for fibromyalgia syndrome: A meta-analysis examining six core symptoms. Eur J Pain. 18(8):1067-1080. "Very few drugs in well-designed clinical trials have demonstrated significant relief for multiple FM symptom domains, whereas non-pharmacologic treatments with weaker study designs have demonstrated multidimensional effects. Future therapeutic trials for FM should prospectively examine each of the core domains and should attempt to combine pharmacologic and non-pharmacologic therapies in well-designed clinical trials."

Perrot S, Schaefer C, Knight T et al. 2012. Societal and individual burden of illness among fibromyalgia patients in France: Association between disease severity and OMERACT core domains. BMC Musculoskel Disord. 13(1):22. "In a sample of 88 patients with FM from France, we found that FM poses a substantial economic and human burden on patients and society. FM severity level was significantly associated with patients' health status and core symptom domains."

Perry CP. 2001.  Current concepts of pelvic congestion and chronic pelvic pain.  JSLS 5(2):105-110.  Pelvic congestion is a common contributor of pelvic pain.  Although recognized in the United Kingdom, it is controversial in the United States. [This paper refers to it as a condition, but it is a symptom.  The causes of pelvic congestion include blood and lymph vessel entrapment by myofascial TrPs, and this cause is treatable.  DJS]

Perry, F., P. H. Heller, J. Kamiya and J. D. Levine. 1989. Altered autonomic function in patients with arthritis or with chronic myofascial pain. Pain 39(1):77-84.

Persinger, M. A., S. G. Tiller and S. A. Koren. 1999. Background sound pressure fluctuations(5DB) from overhead ventilation systems increase subjective fatigue of university students during three-hour lectures. Percept Mot Skills 88(2):451-6.

Peterson E, Finkel J 2021. Trigger point injections for axial back pain in adolescents. BMJ Case Rep. Jun 24;14(6):e242727. "Adolescents who participate in athletics or have abnormal musculoskeletal anatomy have higher incidences of back pain than non-athletic peers with normal anatomy. Significant time and money spent in diagnostic evaluations for axial back pain can result in treatment delay causing a subsequent decrease in quality of life. Myofascial trigger points are a commonly overlooked reason for axial back pain. They develop due to an abnormal myoneural connection in the setting of muscle overuse. Trigger point injections are a technically simple intervention that is both diagnostic and therapeutic in alleviating trigger point-mediated back pain. There are few complications from these injections, and they should be considered prior to surgical referral or fluoroscopic-guided interventions."

Peterson EE, Yao C, Sule SD, et al. 2022. The challenges of identifying fibromyalgia in adolescents. Case Rep Pediatr. Apr 8;2022:8717818. "There are no current diagnostic criteria for fibromyalgia in children to guide clinicians in recognition, thus leading to many subspecialty referrals and extensive imaging and tests…. This case series suggests the need for an updated diagnostic tool for pediatric fibromyalgia to facilitate recognition and treatment."

Peterson JA, Bemben MG, Larson RD, Pereira H, Crowson HM, Black CD. Symptomatic but not asymptomatic COVID-19 impairs conditioned pain modulation in young adults. J Pain. 2022 Jul 21; Online ahead of print. "Pain is a common symptom reported in COVID-19 patients. Impaired endogenous pain-modulatory mechanisms such as conditioned pain modulation (CPM), and exercise-induced hypoalgesia (EIH) have been found in chronic pain conditions but is often overlooked in acute conditions that evoke painful symptoms, such as COVID-19. The purpose was to compare pressure-pain sensitivity, CPM, and EIH function among individuals who previously had COVID-19, both symptomatically and asymptomatically, and a healthy control group…. CPM was impaired in individuals who had symptomatic COVID-19, which may have long-term implications on pain modulation."

Petra AI, Panagiotidou S, Stewart JM et al. 2014. Spectrum of mast cell activation disorders. Expert Rev Clin Immunol. [May 1 Epub ahead of print.] "Mast cell (MC) activation disorders present with multiple symptoms including flushing, pruritus, hypotension, gastrointestinal complaints, irritability, headaches, concentration/memory loss and neuropsychiatric issues. These disorders are classified as: cutaneous and systemic mastocytosis with a c-kit mutation and clonal MC activation disorder, allergies, urticarias and inflammatory disorders and mast cell activation syndrome (MCAS), idiopathic urticaria and angioedema. MCs are activated by IgE, but also by cytokines, environmental, food, infectious, drug and stress triggers, leading to secretion of multiple mediators. The symptom profile and comorbidities associated with these disorders, such as chronic fatigue syndrome and fibromyalgia, are confusing. We propose the use of the term 'spectrum' and highlight the main symptoms, useful diagnostic tests and treatment approaches." [These interactive conditions may be much more common than now suspected. DJS]

Petrofsky J, Laymon M, Lee H. 2019. Local heating of trigger points reduces neck and plantar fascia pain. J Back Musculoskelet Rehabil. [Sep 20 Epub ahead of print] "The effect of single cell heat on trigger points of the body on pain relief was significantly better in the heat groups than in the sham groups. This finding is significant because using heat on trigger points could be an alternative to dry needling performed by healthcare professionals. This modality is a perfect alternative for home use and avoids opioids." [Why must everything be an either/or proposition? The pain from even one trigger point can be considerable. The pain from many, amplified by FM, can be intense and disabling. TrP therapy can minimize pain and dysfunction if the perpetuating factors are addressed. Often, perpetuating factors are co-existing conditions that cannot be eliminated. All options for pain relief should be considered. DJS]

Pettit NJ, Auvenshine RC. 2018. Change of hyoid bone position in patients treated for and resolved of myofascial pain. Cranio. 31:1-17. [Epub ahead of print] "The purpose of this study was to investigate change in hyoid bone position for patients suffering from myofascial pain and to evaluate the modified hyoid triangle as a three-dimensional cephalometric modality for measuring hyoid position.... Changes in dimensions of the hyoid triangle were analyzed with the t-test for paired comparisons..... Statistical analysis showed a drawing nearer of the chin to the third cervical vertebra ...and a release of the hyoid bone away from the floor of the mouth.... These findings suggest resolution of myofascial pain may correlate with decreased forward head posture and relaxation of suprahyoid musculature. The potential for change in oropharyngeal dimension and airway is evident." [Travell and Simons explained the necessity of maintain resting tongue position at the roof of the mouth, behind the front top teeth, to align the hyoid bone. DJS]

Petzke F, Harris RE, Williams DA et al. 2005.  Differences in unpleasantness induced by experimental pressure pain between patients with fibromyalgia and healthy controls.  Eur J Pain 9(3):325-335.  “Patients with FM unexpectedly display less relative unpleasantness than healthy controls in response to random noxious pressure stimuli.  These results are consistent with the concept that chronic pain may reduce the relative unpleasantness of evoked pain sensations.”  Sensitivity to pain and pain tolerance are different.  Patients may have hyperalgesia, a heightened sensitivity toward pain, but still have a greater tolerance to pain.  This difference has not been specified in most previous research.

Peyron, R., L. Garcia-Larrea, M. C. Gregoire, N. Costes, P. Convers, F. Lavenne, F. Mauguiere, D. Michel and B. Laurent. 1999. Haemodynamic brain responses to acute pain in humans:sensory and attentional networks. Brain 122(Pt 9):1765-1780. .

Phan V, Shah J, Tandon H et al. Myofascial pain syndrome: A narrative review identifying inconsistencies in nomenclature. PM R. 2019 Nov 17. [Epub ahead of print] "There is currently confusion surrounding the phenotype of and diagnostic criteria for myofascial pain syndrome (MPS) in the published literature. This narrative literature review investigated whether there is consensus regarding the descriptive terminology used for MPS and the trend of MPS publications over time. The phrase "myofascial pain syndrome" was used to search PubMed and Web of Science, returning 923 articles. Of these, we included full-text, primary research articles containing "myofascial pain syndrome" in the title, reducing the total articles reviewed to 167. We identified 116 descriptors and categorized them under one of five clusters that shared similar findings and are commonly associated with MPS: "trigger points", "muscle", "pain", "nervous system", and "fascia". The frequency of Travell and Simons criteria was tabulated. Terms pertaining to the clusters "trigger points", "muscle", or "pain" appeared in approximately 90% of the articles, "nervous system" in 46%, and "fascia" in 20%. Only 42% used Travell and Simons criteria. Most articles (122) included a combination of three or four clusters to describe MPS. Additionally, MPS publications have doubled since 2010 compared to the prior decade. The publication patterns, determined by changes in which specialty journals MPS manuscripts have been published, have shifted from investigational to intervention studies. This may have been influenced by heterogeneity in the usage of MPS terminology. This underscores the lack of a reliable MPS diagnosis and limits human subjects research. Improved consistency in terminology is needed to establish consensus within the field and inform future research studying the pathophysiology of MPS." [I use "Chronic Myofascial Pain and Dysfunction (CMPD)", to avoid "MPS" used by so many psychologists, dentists etc. as a synonym for TMJD), and specify Travell and Simons' TrP criteria. DJS]

Phillips, S.M. and B.B. Sherwin. 1992. Effects of estrogen on memory function in surgically menopausal women. Psychoneuroendocrinology 17(5):485-95.

Phillips, S. M. and B. B. Sherwin. 1992. Variations in memory function and sex steroid hormones across the menstrual cycle. Psychoneuroendocrinology 17(5):497-506.

Picavet HS, Hoeymans N.  2004.  Health related quality of life in multiple musculoskeletal disease SF-36 and EQ-5D in the DMC3 study.  Ann Rheum Dis. 63(6):723-729.  This study included patients with osteoarthritis, fibromyalgia, rheumatoid arthritis and osteoporosis.  “The co-existence of musculoskeletal diseases should be taken into account in research and clinical practice because of its high prevalence and its substantial impact on health related quality of life.”

Picelli A, Buzzi MG, Cisari C et al. 2016. Headache, low back pain, other nociceptive and mixed pain conditions in neurorehabilitation. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation. Eur J Phys Rehabil Med. [Nov 10 Epub ahead of print.] "Pain is a disabling symptom and is often the foremost symptom of conditions for which patients undergo neurorehabilitation. We systematically searched the PubMed and Embase electronic databases for current evidence on the frequency, evolution, predictors, assessment, and pharmacological and non-pharmacological treatment of pain in patients with headache, craniofacial pain, low back pain, failed back surgery syndrome, osteoarticular pain, myofascial pain syndrome, fibromyalgia, and chronic pelvic pain. Despite the heterogeneity of published data, consensus was reached on pain assessment and management of patients with these conditions and on the utility of a multidisciplinary approach to pain therapy that combines the benefits of pharmacological therapy, physiotherapy, neurorehabilitation, and psychotherapy. We of the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) suggest a need to conduct randomized controlled trials on the efficacy of pain treatments and their risk-benefit profile for the conditions we have reviewed". Free Article [Perhaps such studies may reveal that many patients have many or all of these conditions. DJS]

Picelli A, Ledro G, Turrina A et al. 2011. effects of myofascial technique in patients with subacute whiplash associated disorders: a pilot study. Eur J Phys Rehabil Med 47(4):561-568. "Myofascial techniques may be useful for improving treatment of subacute whiplash associated disorders also reducing their economic burden."

Pickering G, Macian N, Delage N et al. 2018. Milnacipran poorly modulates pain in patients suffering from fibromyalgia: a randomized double-blind controlled study. Drug Des Devel Ther. 12:2485-2496. "Milnacipran did not display a significant analgesic effect after 1-month treatment, but the tendency of milnacipran to reactivate CPM (conditioned pain modulation) in a number of patients must be explored with longer treatment duration in future studies and pleads for possible sub-types of fibromyalgia patients."

Pieczenik SR, Neustadt J. 2007.  Mitochondrial dysfunction and molecular pathways of disease.  Exp Mol Pathol. [Jan 17 Epub ahead of print]  This study proposes that many conditions, including fibromyalgia, have “...underlying pathophysiological mechanisms in common, namely reactive oxygen species (ROS) production, the accumulation of mitochondrial DNA (mt DNA) damage, resulting in mitochondrial dysfunction.. Antioxidant therapies hold promise for improving mitochondrial performance.”  The authors suggest that clinicians consider testing urinary organic acids to determine how best to treat these patients.

Pierson MJ. 2011. Changes in temporomandibular joint dysfunction symptoms following massage therapy: a case report. Int J Ther Massage Bodywork. 4(4):37-47. "Ten 45-minute massage therapy treatments were administered over a five-week period. The client's progress was monitored by an initial, midway, and final assessment, using range of motion testing, personal interview, an orthopedic test, and postural analysis.....The client participated in a home care routine consisting of stretches, self-massage, postural training, a proprioception exercise, and hydrotherapy.....Results include an increase in maximal opening from 3.1 cm to 3.8 cm, an overall increase in neck range of motion, a decrease in muscle hypertonicity using the Wendy Nickel's Scale, a decrease in pain from 7/10 to 3/10 on a numerical pain scale, and a decline in stress. [TMJD is often due to TrPs, and this combination of therapies deserves further study. DJS]

Pimentel M, Park S, Mirocha J et al. 2006.  The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial.  Ann Intern Med. 145(8):557-563.  “Rifaximin [Xifaxan] improves IBS symptoms for up to 10 weeks after the discontinuation of therapy.”

Pinals RS. 2015. Peggy's pain and the creation of Gone With The Wind. Reg Anesth Pain Med. 40(4):384-387. "Margaret Mitchell (1900-1949), author of the best-selling novel Gone with the Wind, had chronic, widespread pain for most of her adult life. …During her life, her diagnoses were problematic and remain so now, but would most likely include fibromyalgia and irritable bowel syndrome."

Pinals RS, Hassett AL. 2013. Reconceptualizing John F. Kennedy's Chronic Low Back Pain. Reg Anesth Pain Med. [Jul 29 Epub ahead of print]. "When the medical records for John Fitzgerald Kennedy were made public, it became clear that the 35th President of the United States suffered greatly from a series of medical illnesses from the time he was a toddler until his assassination in November of 1963. Aside from having Addison disease, no condition seemed to cause him more distress than did his chronic low back pain. A number of surgical procedures to address the presumed structural cause of the pain resulted in little relief and increased disability. Later, a conservative program, including trigger point injections and exercises, provided modest benefit. Herein, the mechanisms underlying his pain are evaluated based on more contemporary pain research. This reconceptualizing of John Fitzgerald Kennedy's pain could serve as a model for other cases where the main cause of the pain is presumed to be located in the periphery."

Pinto Fiamengui LM, Freitas de Carvalho JJ, Cunha CO et al. 2013. The influence of myofascial temporomandibular disorder pain on the pressure pain threshold of women during a migraine attack. J Orofac Pain. 27(4):343-349. Thirty-four women between the ages of 18-60 were separated into a group with migraine and one with migraine and myofascial pain, that later category being assumed as the same as temporomandibular pain. The pressure pain threshold (PPT) on the masseter, anterior temporalis, and Achilles tendon were taken by algometer when the patients were pain free, and during a migraine. "Results: Significantly lower PPT values were found during the migraine attack, especially for women with concomitant myofascial pain, regardless of the side of the reported pain. Conclusion: Migraine attack is associated with a significant reduction in PPT values of masticatory muscles, which appears to be influenced by the presence of myofascial TMD pain." [Dentists, and psychologists, must become aware of pain and dysfunction-generating TrPs that can occur over the whole body, so that they cease the confusing use of "myofascial pain" as synonymous with TMJD. DJS]

Pinto SM, Cheung JPY, Samartzis D et al. 2020. Differences in proprioception between young and middle-aged adults with and without chronic low back pain. Front Neurol. Dec 21;11:605787. "Young adults with CLBP, and middle-aged adults with and without CLBP had inferior proprioceptive reweighting capability. This finding may indicate potential age-related deterioration in central and peripheral processing of lumbar proprioceptive signals. Future studies should use advanced imaging and/or electroencephalogram to determine mechanisms underlying changes in proprioceptive reweighting in middle-aged adults."

Piraccini E, Calli M, Taddei S et al. 2020. Erector spinae plane block and rhomboid intercostal block for the treatment of post-mastectomy pain syndrome. Saudi J Anaesth. Oct-Dec;14(4):517-519. "Post-mastectomy pain syndrome (PMPS) can have multiple pain generators, including neuropathic pain and myofascial pain syndrome (MPS). Erector spinae plane (ESP) block and rhomboid intercostal block (RIB) have been used to provide anesthesia of the thorax and also for some chronic pain conditions. We describe a 43-year-old (woman) suffering from right PMPS after right mastectomy, full axillary, and mammary lymph node dissection. We treated her with ESP blocks and RIB to reduce neuralgia and MPS: Neuropathic pain disappeared and the patient experienced only slight residual pain. The result was maintained 3 months later. This report suggests that ESP block and RIB with local anesthetic and corticosteroids with might be useful to treat a PMPS."

Piras C, Conte S, Pibiri M, et al. 2020. Metabolomics and psychological features in fibromyalgia and electromagnetic sensitivity. Sci Rep. Nov 24;10(1):20418. "Fibromyalgia (FM) as Fibromyalgia and Electromagnetic Sensitivity (IEI-EMF) are a chronic and systemic syndrome. The main symptom is represented by strong and widespread pain in the musculoskeletal system. The exact causes that lead to the development of FM and IEI-EMF are still unknown. Interestingly, the proximity to electrical and electromagnetic devices seems to trigger and/or amplify the symptoms. We investigated the blood plasma metabolome in IEI-EMF and healthy subjects using 1H NMR spectroscopy coupled with multivariate statistical analysis…. No significant differences between IEI-EMF and controls relative to personality aspects, Locus of Control, and anxiety were found. Multivariate statistical analysis on the metabolites identified by NMR analysis allowed the identification of a distinct metabolic profile between IEI-EMF and healthy subjects. IEI-EMF were characterized by higher levels of glycine and pyroglutamate, and lower levels of 2-hydroxyisocaproate, choline, glutamine, and isoleucine compared to healthy subjects. These metabolites are involved in several metabolic pathways mainly related to oxidative stress defense, pain mechanisms, and muscle metabolism."

Pirri C, Fede C, Fan C, et al. 2021. Ultrasound imaging of head/neck muscles and their fasciae: An observational study. Front Rehabil Sci. 2021 Dec 15;2:743553. "Ultrasound imaging is a suitable and reliable tool to study the muscles and fasciae of the head and neck region, permitting also the evaluation of the ability of the muscles to contract. Finally, identifying functional asymmetry that could become symptomatic, US imaging could allow an early rehabilitation treatment."

Pirri C, Fede C, Petrelli L, et al. Immediate effects of extracorporeal shock wave therapy in fascial fibroblasts: An in vitro study. Biomedicines. 2022 Jul 18;10(7):1732. "The aim of this study was to investigate changes in cell biology of fibroblasts derived from deep/muscular fascia following treatment with ESWs…. This study demonstrated for the first time that ESWs can lead to in vitro production of hyaluronan-rich vesicles immediately after the treatment…. These in vitro data indicate that fascial cells respond to ESW treatment by regulating and remodeling the formation of extracellular matrix" [This may indicate the mechanism by which extracorporeal shock wave therapy affects MTrPs. DJS]

Pizzigallo, E., D. Racciatti and J. Vecchiet.1999. Clinical and path of physiological aspects of chronic fatigue syndrome. J Musculoskel Pain 7(1-2):217-224.

Plaut S. Suggesting a mechanism for acupuncture as a global percutaneous needle fasciotomy that respects tensegrity principles for treating fibromyalgia. Front Med (Lausanne). 2023 Jan 27;9:952159. "A recent study suggested a theoretical model (coined "Fascial Armoring") with a cellular pathway to help explain the pathogenesis of myofascial pain/fibromyalgia syndrome and functional psychosomatic syndromes. It proposes that these syndromes are a spectrum of a single medical entity that involves myofibroblasts with contractile activity in fascia and aberrant extracellular matrix (ECM) remodeling, which may lead to widespread mechanical tension and compression…Previous studies show that a mechanical action by needling induces soft tissue changes and lowers the shear modulus and stiffness in myofascial tissue."

Plavnik K, Tenaglia A, Hill C et al. 2019. A novel, non-opioid treatment for chronic pelvic pain in women with previously treated endometriosis utilizing pelvic floor musculature trigger point injections and peripheral nerve hydrodissection. PM R. [Oct 4 Epub ahead of print] Sixteen female patients with biopsy confirmed endometriosis were given ultrasound-guided pelvic floor trigger point injections and peripheral nerve hydrodissection performed once a week for six weeks…. Analysis suggests the treatment was effective at relieving pain related to endometriosis; it also reflected promise in improving overall pelvic function, particularly in relation to intercourse, working and sleeping. [It is an advance that the local TrPs are being treated and identified as the cause of pain. These patients did not have CMPD nor did they have FM. When chronic pain presents, an assessment for TrPs elsewhere is warranted, as latent TrPs may be causing dysfunctions. DJS]

Plazier M, Dekelver I, Vanneste S et al. 2013. Occipital nerve stimulation in fibromyalgia: A double-blind placebo-controlled pilot study with a six-month follow-up. Neuromodulation. [Oct 7 Epub ahead of print]. "The goal of this study is to evaluate the effectiveness of occipital nerve stimulation (ONS) as a surgical treatment for fibromyalgia in a placebo-controlled design….Eleven patients were selected based on the American College of Rheumatology-90 criteria and implanted with an occipital nerve trial-lead stimulator. Baseline scores for pain, mood, and fatigue were acquired, and patients were randomized in a ten-week double-blinded crossover design with placebo and effective subsensory threshold stimulation (no paresthesias). After finalizing the trial, nine patients were implanted permanently; evaluation was performed prior to surgery and at six months after surgery for pain, fatigue, and mood of the number of trigger points and overall morbidity. Significant results were found during the trial for a decrease in pain intensity (39.74%) on visual analogue scale …and pain catastrophizing scale (PCS) during effective stimulation. A total of 9/11 patients responded to trial treatment; however, in two patients, this might be a placebo effect, recognizable due to the study design. Six months after permanent implantation, pain intensity remained decreased (44.01%) on VAS…. Besides the VAS, significant changes were noted for PCS, fatigue (modified fatigue impact scale), the number of trigger points, and overall morbidity (fibromyalgia impact questionnaire). There were no serious adverse events. Our data strongly suggest that ONS is beneficial in the treatment of fibromyalgia. The beneficial effects are stable at six months after permanent implantation. Subsensory threshold stimulation is feasible in designing a placebo-controlled trial." [Although the authors recognize the importance of the "trigger point count", they fail to recognize the trigger points as the actual generators of pain and dysfunction. Perhaps if the trigger points had been treated and perpetuating factors identified and controlled, the surgery would not have been necessary. Then again, the surgery might have taken care of some of the perpetuating factors. We will not know, because the authors did not understand the role of the trigger points. DJS]

Plazier M, Ost J, Stassijns G et al. 2014. Pain characteristics in fibromyalgia: understanding the multiple dimensions of pain. Clin Rheumatol. [Jul 22 Epub ahead of print.] "Fibromyalgia is a common disease with a high economic burden. The etiology of this disease remains unclear, as there are no specific abnormalities on clinical or technical examinations. Evidence suggests that central pain sensitization at the brain pain matrix might be involved. Understanding the pain characteristics of this disease is of importance both for diagnosis and treatment. … We were able to define pain characteristics in this group of patients. The reciprocal effects of mood and fatigue on pain experience could be identified within the data; catastrophizing scores show a high correlation with overall life quality and pain experience. We have performed a cluster analysis on the fibromyalgia patients, based on the four main principal components defining the overall disease burden. Mood explained most of the variance in symptoms, followed by mental health state, fatigue, and catastrophizing. Three clusters of patients could be revealed by these components. Clusters: 1) high scores on mood disorders, pain, and decreased mental health, 2) high scores on fatigue and physical health, and 3) a mixture of these two groups. This data suggest that different subgroups of fibromyalgia patients could be identified and based on that, treatment strategies and results might be adapted."

Pleman B, Park M, Han X et al. 2019. Mindfulness is associated with psychological health and moderates the impact of fibromyalgia. Clin Rheumatol. [Jan 14 Epub ahead of print] "Higher mindfulness is associated with less pain interference, lower impact of fibromyalgia, and better psychological health and quality of life in people with fibromyalgia. Mindfulness moderates the influence of fibromyalgia impact on anxiety, suggesting mindfulness may alter how patients cope with fibromyalgia. Future studies should assess how mind-body therapies aiming to cultivate mindfulness may impact the well-being of patients with fibromyalgia."

Plog BA, Nedergaard M. 2017. The glymphatic system in central nervous system health and disease: Past, present, and future. Annu Rev Pathol. [Dec 1 Epub ahead of print] "The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudolymphatic function in the brain.... Here, we review the role of the glymphatic pathway in CNS physiology, the factors known to regulate glymphatic flow, and the pathologic processes in which a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, are also discussed." [The glymphatic system could be involved in central sensitization, sleep dysfunction, cognitive deficits, and several other aspects of FM. DJS]

Plotnikoff GA. 2003.  Food as medicine – cost-effective health care?  The example of omega-3 fatty acids.  Minn Med 86(11):41-5.  This very interesting article notes that the US spends over half of the amount of money spent on pharmaceuticals in the world, yet our health care is not the best in many areas.  It proposes that it is in the best interest to look first at non-pharmaceutical methods to promote health, such as healthy food.


Plotnikoff GA, Quigley JM. 2003.  Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain.  Mayo Clin Proc 78(12):1463-1470.  This study showed that vitamin D deficiency was present in 93% of consecutive patients with nonspecific muscle pain, no matter the season.

Plotsky, O. M. 1998. Stress system plasticity: neural adaptations to neonatal pain and stress. J Musculoskel Pain 6(3):57-60.

Poelmans J, Feenstra L, Tack J. 2005.  The role of (duodeno)gastroesophagopharyngeal reflux in unexplained excessive throat phlegm.  Dig Dis Sci. 50(5):824-832.  “Unexplained excessive throat phlegm is a sign suggestive of GER and GEPR, and unexplained yellow throat phlegm a sign suggestive of duodenogastroesophagopharyngeal reflux (DGEPR).”

Pogatzki-Zahn EM, Englbrecht JS, Schug SA. 2009.  Acute pain management in patients with fibromyalgia and other diffuse chronic pain syndromes.  Curr Opin Anaesthesiol. [Jul 13 Epub ahead of print].  Adequate pain management of acute pain is of vital necessity for patients with the central sensitization of FM.  [It is also of vital necessity for others to help prevent FM central sensitization. DJS]

Polat A, Ekinci O, Terzioglu B et al. 2011. Treatment of lateral epicondylitis using betahistine dihydrochloride. J Musculoskel Pain. 19(4):201-206. The description of lateral epicondylitis is often given to pain in the area caused by myofascial TrPs, and TrP twitch causes excess histamine at the motor endplate. Betahistadine is a histamine agonist. Interesting. DJS]

Polat M, Kahveci A, Tecer D, et al. The role of ultrasonographic synovial assessment in rheumatoid arthritis patients with concomitant fibromyalgia. Arch Rheumatol. 2022 Sep 20;38(2):174-182. Synovial inflammation is a prominent sign in RA patients diagnosed with FM according to the 2016 ACR FM diagnostic criteria. The higher disease activity seen in the presence of FM in RA patients is associated with FM rather than synovitis.

Poli-Neto OB, Martins Chamochumbi CC, Toscano P et al. 2018. Electromyographic characterization of abdominal wall trigger points developed after caesarean section and response to local anaesthesia: an observational study. BJOG. [Feb 27 Epub ahead of print] "Trigger points developed after caesarean section, even without clinical symptoms or signs of neuralgia, may originate from neuropathies. Electromyographic abnormalities were associated with pain remission after anesthesia injection; normal electromyography findings were associated with undiagnosed causes of pain such as adhesions.

Polli A, Hendrix J, Ickmans K, et al. 2022. Genetic and epigenetic regulation of Catechol-O-methyltransferase in relation to inflammation in chronic fatigue syndrome and fibromyalgia. J Transl Med. 2022 Oct 25;20(1):487. "Catechol-O-methyltransferase (COMT) has been shown to influence clinical pain, descending modulation, and exercise-induced symptom worsening. COMT regulates nociceptive processing and inflammation, key pathophysiological features of Chronic Fatigue Syndrome and Fibromyalgia (CFS/FM)... MB-COMT DNA methylation might be an independent factor contributing to the pathophysiology of CFS/FM. Further research on DNA methylation in complex conditions such as CFS/FM is warranted."

Pomares FB, Roy S, Funck T et al. Up-regulation of cortical GABAA receptor concentration in fibromyalgia. Pain. 2019 Sep 27. [Epub ahead of print] "This study shows increased GABAA receptor concentration in FM, associated with pain symptoms and impaired function. The changes were widespread and not restricted to pain-processing regions. These findings suggest that the GABAergic system is altered, possibly indicating an imbalance between excitatory and inhibitory neurotransmission."

Pongratz D, Spath M. 2001.  [What helps in back pain? Guideline for symptomatic therapy] MMW Fortschr Med. 143(18):26-29. [German]  “Both in acute and chronic, unspecific back pain, the myofascial pain syndrome resulting in muscular dysbalance is a major factor.  For the differential diagnosis, however, consideration must always be given to concomitant symptoms (neurological deficits, general symptoms, signs of osteopathy).  Pathophysiologically, the active trigger point corresponds to a contraction in the muscle fibers that forms in the region of the a neuromuscular endplate, and leads, via biochemical processes, to the stimulation of mesochymal nociceptors.  Symptomatic treatment of acute and chronic back pain may be broken down into a) physical measures, b) local therapeutic regimens, and c) systemic pharmacotherapy.  As medication, non-steroidal anti-inflammatory drugs, non-opioid analgesics, opioids analgesics, muscle relaxants, and antidepressives are available, and are dose-matched to the severity and stage of the condition.  The spectrum of therapeutic options is outlined.”


Pongratz DE, Spath M. 1998.  [Myofascial pain syndrome – frequent occurrence and often misdiagnosed]  Fortschr Med. 116(27):24-29.  “The difference between trigger points (MPS) and tender points (fibromyalgia) is of central importance – not merely in a linguistic sense.  Knowledge of the signs and symptoms typically associated with a trigger point often obviates the need for time-consuming and expensive technical diagnostic measures.  The assumption that many cases of unspecific complaints affecting the musculoskeletal system may be ascribed to MPS makes clear the scope for the saving of costs.”


Pongratz DE, Vorgerd M, Schoser BGH. 2004.  Scientific aspects and clinical signs of muscle pain.  J Musculoskeletal Pain 12(3/4):121-128.  This article highlights painful muscle disorders, including the myopathological aspects of inflammatory and metabolic conditions.  Exercise intolerance is a common symptom of many of them, due to their impact on muscle energy metabolism.  MPS due to TrPs is a more common cause of muscle pain, with morphological changes noted as contraction discs often located in the motor endplate area.  [Due to the localized energy depletion of these states, including TrPs, it is logical that the impact of TrPs would be especially devastating in a patient who had a co-existing condition that already depleted the energy state, such as the mitochondrial ATP affect of FMS.  DJS]

Pongratz DE, Spath M. 1998.  [Myofascial pain syndrome – frequent occurrence and often misdiagnosed].  Fortschr Med 116(27):24-9.[German]

Pongratz, D. E, and M. Spath. 1997.  Morphologic aspects of muscle pain syndromes: a critical review. Myofascial pain–update in diagnosis and treatment.  Phys Med Rehab Clin North Am 8(1): 55-68.

Ponikau JU, Sherris DA, Weaver A et al. 2005.  Treatment of chronic rhinosinusitis with intranasal amphotericin B: a randomized, placebo-controlled, double-blind pilot trial.  J Allergy Clin Immunol. 115(1):125-131.  “Intranasal amphotericin B reduced inflammatory mucosal thickening on both CT scan and nasal endoscopy and decreased the levels of intranasal markers for eosinophilic inflammation in patients with CRS.”  Ampho B nasal spray may be an effective and relatively safe treatment for chronic fungal sinusitis.

Pontari M, Giusto L. 2013. New developments in the diagnosis and treatment of chronic prostatitis/chronic pelvic pain syndrome. Curr Opin Urol. 23(6):565-569. "Symptoms in men with chronic prostatitis/CPPS appear to cluster into a group with primarily pelvic or localized disease, and a group with more systemic symptoms. Several other chronic pain conditions can be associated with chronic prostatitis/CPPS, including irritable bowel syndrome, fibromyalgia, and chronic fatigue syndrome. Markers of neurologic inflammation and autoimmune disease parallel changes in symptoms after treatment. Treatment options include new alpha-blockers, psychological intervention, and prostate-directed therapy. The areas of acupuncture and pelvic floor physical therapy/myofascial release have received increased recent attention and appear to be good options in these patients. Future therapy may include antibodies to mediators of neurogenic inflammation and even treatment of bacteria in the bowel….The diagnosis of chronic prostatitis/CPPS must include conditions traditionally outside the scope of urologic practice but important for the care of men with chronic pelvic pain. The treatment is best done using multiple simultaneous therapies aimed at the different aspects of the condition."

Ponte CD, Johnson-Tribino J. 2005.  Attitudes and knowledge about pain: an assessment of West Virginia family physicians.  Fam Med. 37(7):477-480.  “Chronic nonmalignant pain and assessing pain in the elderly are problematic for many physician providers.  Perceived regulatory scrutiny does impact physician prescribing of opioids for patients in pain.  The majority of respondents felt that their formal medical training did not prepare them to effectively manage pain.”

Popkirov S, Enax-Krumova EK, Mainka T, et al. 2020. Functional pain disorders - more than nociplastic pain. NeuroRehabilitation. Sep 20 Online ahead of print. "Chronic back pain, fibromyalgia syndrome and complex regional pain syndrome are best understood within a biopsychosocial framework of pain perception that considers structural factors (predispositions and sequelae) and psychobehavioral mechanisms. Although pain is often the primary complaint, it should not be the only focus of treatment, as accompanying symptoms such as sleep or mood problems can significantly impact quality of life and offer useful leverage points for multimodal treatment. Analgesic pharmacotherapy is rarely helpful on its own, and should always be imbedded in a multidisciplinary setting".

Poppler LH, Mackinnon SE. 2018. The role of the peripheral nerve surgeon in the treatment of pain. Neurotherapeutics. [Dec 12 Epub ahead of print] "Many physicians find these patients challenging because they often have complicated histories, emotional comorbidities, confusing examinations, difficult problems to fix, and the possibility of factitious complaints for attention or narcotic pain medications. As a result, many patients are lumped into the category of chronic, centralized pain and relegated to pain management. However, recent literature suggests that surgical management of carefully diagnosed generators of pain can greatly reduce patients' pain and narcotic requirements. This article reviews recent literature on surgical management of pain and four specific sources of chronic pain amenable to surgical treatment: painful neuroma, nerve compression, myofascial/musculoskeletal pain, and complex regional pain syndrome type II."

Porcelli MJ. 2004.  Why are our patients still in pain? Finding a balance in treating patients for nonmalignant pain.  J Am Osteopath Assoc. 104(2):73-75, 66.  “Are physicians doing patients harm by allowing them to remain in chronic pain?  Conversely, are physicians doing patients harm by supporting a dependence on pain-relieving medication that allows normal functions of daily life? There is a delicate balance that each physician must find in the context of his or her practice of medicine.”

Portelli A, Reid SA. 2018. Cervical proprioception in a young population who spend long periods on mobile devices: A 2-Group Comparative Observational Study. J Manipulative Physiol Ther. [Jan 12 Epub ahead of print] "The purpose of this study was to evaluate if young people with insidious-onset neck pain who spend long periods on mobile electronic devices (known as "text neck") have impaired cervical proprioception and if this is related to time on devices.....The participants with text neck had a greater proprioceptive error during cervical flexion compared with controls. This could be related to neck pain and time spent on electronic devices." [The presence of trigger points may be a contributor of "text neck", and not just in the young. DJS]

Portenoy, R. K., V. Dole, H. Joseph, J. Lowinson, C. Rice, S. Segal and B. L. Richman. 1997.  Pain management and chemical dependency.  Evolving perspectives.  JAMA 278(7):592-593.

Portenoy, R. K. 1996.  Opioid therapy for chronic nonmalignant pain: a review of the critical issues.  J Pain Symptom Manage 11(4):203-217.

Portenoy RK. 2000.  Current pharmacotherapy of chronic pain.  J Pain Symptom Manage 19(1 Suppl):S16-S20.  “The combination of opioids and other drugs, such as an N-methyl-D-aspartate-receptor antagonist, may improve the balance between analgesia and adverse effects.”

Portenoy RK, Ugarte C, Fuller I et al. 2004.  Population-based survey of pain in the United States: differences among white, African American, and Hispanic subjects.  J Pain 5(6):317-328.  “Neither race nor ethnicity predicted disabling pain, but the minorities had more characteristics identified as predictors.  The data suggest that race and ethnicity contribute to clinical diversity, but socioeconomic disadvantage is the more important predictor of disabling pain.  Race and ethnicity influence the presentation and treatment of chronic pain.  Pain was highly prevalent across groups, and there were racial and ethnic differences in pain experience and treatment preferences.”

Porter FL, Wolf CM, Miller JP. 1999.  Procedural pain in newborn infants: the influence of intensity and development.  Pediatrics 104(1):e13.  “Newborn and developing infants show increased magnitude physiologic and behavioral responses to increasingly invasive procedures, demonstrating that even very prematurely born infants respond to pain and differentiate stimulus intensity.  The best approach may be one of universal precaution to provide pain management systematically to reduce the acute and long-term impact of early procedural pain, development, stimulus intensity, pain response.”

Porter, F. L., R. E. Grunau and K. J. Anand. 1999.  Long-term effects of pain in infants.  J Dev Behav Pediatr 20(4):253-61.

Post, L. F., J. Blustein, E. Gordon and N. N. Dubler. 1996. Pain: ethics, culture, and informed consent to relief. J Law Med & Ethics 24(4):348-59.

Potenzieri C, Undem BJ. 2011. Basic mechanisms of itch. Clin Exp Allergy. [Jun 6. doi: 10.1111/j.1365-2222.2011.03791.x. Epub ahead of print]. "Studies have demonstrated that both peripheral and central sensitization to pruritogenic stimuli occur during chronic itch."

Potter M, Schafer S, Gonzalez-Mendez E et al. 2001.  Opioids for chronic nonmalignant pain.  Attitudes and practices of primary care physicians in the UCSF/Stanford Collaborative Research Network.  University of California, San Francisco.  J Fam Pract 50(2):145-151.  “Primary care physicians are willing to prescribe schedule III opioids as needed, but many are unwilling to use schedule II opioids around the clock for CNMP.  Individual prescribing practices vary widely among primary care physicians.  Concerns about physical dependence, tolerance, and addiction are barriers to the prescription of opioids by primary care physicians for patients with CNMP.”

Potts J, Payne RE. 2007.  Prostatitis: infection, neuromuscular disorder, or pain syndrome?  Proper patient classification is key.  Cleve Clin J Med. 74 Suppl 3:S63-71. “Prostatitis is a broad term used to describe inflammation of the prostate that may be associated with a myriad of lower urinary tract symptoms of sexual discomfort and dysfunction.”  “Prostatitis is classified into four categories, including acute and chronic bacterial forms, a chronic abacterial form, and an asymptomatic form.”  “Chronic abacterial prostatitis (also known as chronic pelvic pain syndrome) is both the most prevalent form and also the least understood and the most challenging to evaluate and treat.  This form of prostatitis may respond to non-prostate-centered treatment strategies such as physical therapy, myofascial trigger point release, and relaxation techniques. Because the various forms of prostatitis call for vastly different treatment approaches, appropriate evaluation, testing, and differential diagnosis are crucial to effective management.”

Poulletier de Gannes F., Lagroye I., Haro E et al. 2002. Effects of radio frequencies emitted by mobile phone on CNS cell cultures.  Glia (Suppl 1):S51-52 [Abstract]. Mobile phones at 900 MHz could induce CNS response on the cellular level.

Poveda-Pagan EJ, Lozano-Quijada C, Segura-Heras JV et al. 2017. Referred pain patterns of the infraspinatus muscle elicited by deep dry needling and manual palpation. J Altern Complement Med. Mar 7. [Epub ahead of print] "Objectives: To identify the most common referred pain (ReP) pattern of the infraspinatus myofascial trigger point (MTrP) and compare its coincidence with the original ReP pattern, to verify whether there are any significant differences by sex and types of technique and to determine the observed signs and symptoms evoked by deep dry needling (DDN) and manual palpation (MPal)…. The ReP pattern of the infraspinatus muscle coincides with the original pattern described by Travell and Simons, although the neck area should be questioned."

Powell J. 2014. The Approach to Chronic Pelvic Pain in the Adolescent. Obstet Gynecol Clin North Am. 41(3):343-355. "Adolescents present to outpatient and acute care settings commonly for evaluation and treatment of chronic pelvic pain (CPP). Primary care providers, gynecologists, pediatric and general surgeons, emergency department providers, and other specialists should be familiar with both gynecologic and nongynecologic causes of CPP so as to avoid delayed diagnoses and potential adverse sequelae. Treatment may include medications, surgery, physical therapy, trigger-point injections, psychological counseling, and complementary/alternative medicine. Additional challenges arise in caring for this patient population because of issues of confidentiality, embarrassment surrounding the history or examination, and combined parent-child decision making."

Pradeep A, Birerdinc A, Branigan T, et al. Evidence for an association of serum microanalytes and myofascial pain syndrome. BMC Musculoskelet Disord. 2023 Aug 1;24(1):624. "Cytokine levels significantly correlate with selected clinical assessments. This indirectly suggests possible biological relevance for understanding MPS. Correlations among some cytokine clusters; and DHEA, BDNF kynurenine, NPY, and acetylcholine may act together in MPS. These findings should be further investigated for confirmation that link these microanalytes with select clinical findings in people with MPS."

Pradhan AA 1, Smith ML, McGuire B et al. 2014. Characterization of a novel model of chronic migraine. Pain. 155(2):269-74. "Chronic migraine is a disabling condition that affects hundreds of millions of individuals worldwide. The development of novel migraine treatments has been slow, in part as a result of a lack of predicative animal models. We have developed a new model of chronic migraine involving the use of nitroglycerin (NTG), a known migraine trigger in humans. Chronic intermittent administration of NTG to mice resulted in acute mechanical hyperalgesia with each exposure as well as a progressive and sustained basal hyperalgesia. This chronic basal hyperalgesia occurred in a dose-dependent fashion and persisted for days after cessation of NTG administration. NTG-evoked hyperalgesia was exacerbated by the phosphodiesterase 5 inhibitor sildenafil, also a human migraine trigger, consistent with nitric oxide as a primary mediator of this hyperalgesia. The acute but not the chronic basal hyperalgesia was significantly reduced by the acute migraine therapy sumatriptan, whereas both the acute and chronic hyperalgesia was significantly attenuated by the migraine preventive therapy topiramate. Chronic NTG-induced hyperalgesia is a mouse model that may be useful for the study of mechanisms underlying progression of migraine from an episodic to a chronic disorder, and for the identification and characterization of novel acute and preventive migraine therapies."

Pradhan S, Robin Bansal R, Das A, et al. Osteo-cutaneous trophic changes in complex regional pain syndrome and their reversal with steroids. Neurol India. 2022 May-Jun;70(3):1119-1124. "We came across five patients of CRPS in Out Patient clinics of super-specialty Institutes in North India. All five cases fulfilled the Budapest criteria for the diagnosis of CRPS…. All five cases were found to have excruciating neuropathic pain in defined regions along with cutaneous manifestations. Osseous changes in the form of surface erosion of underlying bones in four cases and marked marrow edema leading to considerable increase in bone thickness in one case were noted. All these features improved considerably following steroid therapy. Bone marrow edema and bone resorption showed improvement on serial imaging…. Apart from pain relief, steroids therapy is capable of reversing the osteo-cutaneous autonomic changes of CRPS type I."

Prados G, Miro E, Martínez MP et al. 2013. Fibromyalgia: gender differences and sleep-disordered breathing. Clin Exp Rheumatol. 31(6 Suppl 79):102-110. "Alterations in sleep respiratory patterns were more highly prevalent in male than in female FM patients. More so in male FM patients, the alterations in sleep patterns, non-refreshing sleep, and other FM-related symptoms observed in this population might be part of a primary sleep-disordered breathing."

Prasanna, A. 1993. Myofascial pain as postoperative complication. J Pain Sympt Manage8(7):450-451.

Prateepavanich, P., V. Kupniratsaikul and T. Charoensak. 1999. The relationship between myofascial trigger points of gastrocnemius muscle and nocturnal calf cramps. J Med Assoc Thai82(5):451-9.

Prato, F. S., J. J. Carson, K. P. Ossenkopp, and M. Kavaliers. 1995. Possible mechanisms by which extremely low frequency magnetic fields affect opioid function. FASEB J 9(9):807-14.

Pratt RL. 2021. Hyaluronan and the fascial frontier. Int J Mol Sci. Jun 25;22(13):6845. "Hyaluronan (hyaluronic acid or HA) is the most abundant polysaccharide of the extracellular matrix of connective tissues. HA can impact cell behavior in specific ways by binding cellular HA receptors, which can influence signals that facilitate cell survival, proliferation, adhesion, as well as migration. … Despite being discovered over 80 years ago, its properties within the world of fascia have only recently received attention…. Recognized interactions between cells and their HA-rich extracellular microenvironment support the importance of studying the relationship between HA and the body's fascial system. From fasciacytes to chronic pain, this review aims to highlight the connections between HA and fascial health."

Prehm P. 2013. Curcumin analogue identified as hyaluronan export inhibitor by virtual docking to the ABC transporter MRP5. Food Chem Toxicol. 62:76-81. Hyaluronan (hyaluronic acid) is produced in excess in many disease states, including metastatic cancers, inflammation, or insufficient blood flow (such as the energy crisis in trigger point areas). Fibroblasts are the most common type of connective tissue cell, and they form hyaluronic acid. Fibroblasts synthesize the extra cellular matrix, collagen, and stroma, which make up the connective tissue framework. Fibroblasts play a critical role in cellular healing. The multidrug resistance associated protein 5 (MRPS 5) transports the hyaluronic acid from the fibroblasts. MRPS 5 is inhibited by the plant phenols curcumin or xanthohumol. The best plant phenol to inhibit hyaluronic acid is hylin. Hylin is found in natural curcumin extracts, such as turmeric. "Since curcumin itself is unstable under physiological conditions, the active component for many cell biological and pharmaceutical effects of natural curcumin preparations could be that hylin that acts by hylauronan inhibition." [This research meshes well with the studies we did on geloid masses in patients with FM and CMP, and indicates that patients with FM and CMP may need to be very careful using any product with hyaluronic acid. HA is a component in many cosmetics, body lotions, and anti-aging formulas. DJS]

Preuss HG, Bagchi D, Bagchi M. 2002.  Protective effects of a novel niacin-bound chromium complex and a grape seed proanthocyanidin extract on advancing age and various aspects of syndrome X.  Ann N Y Acad Sci. 957:250-259.  Chronium or grape seed supplementation may be helpful to control insulin resistance and age-related conditions.

Prevalence of mitral valve prolapse in primary fibromyalgia: a pilot investigation.  Arch Phys Med Rehabil 70(7):541-543.

Prez-Bellmunt A, Casasayas-Cos O, Lopez-de-Celis C, et al. 2021. Effects of dry needling of latent trigger points on viscoelastic and muscular contractile properties: Preliminary results of a randomized within-participant clinical trial. J Clin Med. Aug 27;10(17):3848. "This study aimed to evaluate changes in neuromuscular function and pain perception in latent trigger points (TrPs) in the gastrocnemius muscle after a single session of dry needling…. In conclusion, a single session of dry needling was able to change some parameters of neuromuscular function, such as muscle tone, relaxation, pressure pain sensitivity, and creep in the lateral (but not medial) gastrocnemius but did not improve strength or range of motion."

Price DD, Staud R. 2005.  Neurobiology of fibromyalgia syndrome.  J Rheumatol Suppl. 75:22-28.  “Accumulating evidence suggests that fibromyalgia syndrome (FM) pain is maintained by tonic impulse input from deep tissues, such as muscle and joints, in combination with central sensitization mechanisms.  This nociceptive input may originate in peripheral tissues (trauma and infection) resulting in hyperalgesia/allodynia and/or central sensitization.  Such alterations of relevant pain mechanisms may lead to long term neuroplastic changes that exceed the antinociceptive capabilities of affected individuals, resulting in ever-increasing pain sensitivity and dysfunction.  Future research needs to address the important role of abnormal nociception and/or antinociception for chronic pain in FM.”

Price DD, Zhou Q, Moshiree B et al. 2006.  Peripheral and central contributions to hyperalgesia in irritable bowel syndrome.  J Pain 7(8):529-535.  “Pain in irritable bowel syndrome is likely to be at least partly maintained by peripheral impulse input from the colon/rectum and central sensitization.”  Central sensitization contributes to IBS and is at least partly maintained by peripheral pain stimuli and is in this way similar to FMS.

Price TJ, Gold MS. 2017. From mechanism to cure: Renewing the goal to eliminate the disease of pain. Pain Med. [Oct 25 Epub ahead of print] "Persistent pain causes untold misery worldwide and is a leading cause of disability. Despite its astonishing prevalence, pain is undertreated, at least in part because existing therapeutics are ineffective or cause intolerable side effects. In this review, we cover new findings about the neurobiology of pain and argue that all but the most transient forms of pain needed to avoid tissue damage should be approached as a disease where a cure can be the goal of all treatment plans, even if attaining this goal is not yet always possible….We discuss barriers that are currently hindering the achievement of this goal, as well as the development of new therapeutic strategies. We also discuss innovations in the field that are creating new opportunities to treat and even reverse persistent pain, some of which are in late-phase clinical trials."

Prince PB, Rapaport AM, Sheftell FD et al. 2004.  The effect of weather on headache.  Headache 44(6):596-602.  This study supports the influence of weather changes on headache.

Prior JA, Paskins Z, Whittle R et al. Rheumatological conditions as risk factors for self-harm: A retrospective cohort study. Arthritis Care Res (Hoboken). 2020 Jun 11. [Epub ahead of print] "Patients with ankylosing spondylitis, fibromyalgia, osteoarthritis or rheumatoid arthritis were identified between 1990-2016 and matched to patients without these conditions. Incident self-harm was defined by medical record codes following a rheumatological diagnosis…. Primary care patients with fibromyalgia, osteoarthritis or rheumatoid arthritis (but not ankylosing spondylitis) are at increased risk of self-harm compared to people without these rheumatological conditions. Clinicians need to be aware of the potential for self-harm in patients with rheumatological conditions (particularly fibromyalgia), explore mood and risk with them, and offer appropriate support and management. [It would be interesting to explore the reason for the risk, including perceived hopelessness and/or helplessness due to inadequate pain control options, lack of support network, etc. DJS]

Prist V, De Wilde VA, Masquelier E. 2012. Ann Phys Rehabil Med 55(3):174-189. This case report presents a 49-year old woman suffering from widespread pain since 2002. Her gait pattern included hip adduction, flexed hips and knees and bilateral equines hip deformity. She was diagnosed by several clinicians, but each had a different idea of what she had: fibromyalgia with dystonia, CNS injury, Little's disease, intramedullary spinal cord tumor, or multiple sclerosis. The authors conclude that the logical diagnosis is fibromyalgia with dystonia; the dystonia being due to generalized analgesic protective attitude. [The patient was not assessed for myofascial trigger points. If she had been, by someone well-trained in myofascial medicine, the diagnosis might have been different. Other diagnoses may be involved, and central sensitization is certainly part of this patient's cause of misery, but as to what the cause behind the descriptions are, the TrP assessment and postural analysis must be done to complete the picture. DJS].

Proctor SL, Estroff TW, Empting LD et al. 2012. Prevalence of Substance Use and Psychiatric Disorders in a Highly Select Chronic Pain Population. J Addict Med. [Nov 5 Epub ahead of print]. "Certain populations of patients with complex nociceptive, neuropathic, and myofascial pain syndromes may have a lower prevalence of substance use disorders than the general population. They also have concurrent psychiatric disorders, which should be evaluated and treated concomitantly as part of their chronic pain treatment. Despite the low prevalence of substance use disorders, these patients must be continuously monitored for abuse, misuse, and diversion of their medication. The low prevalence may be attributable to the severity of their illness, the patients' inability to achieve pain relief and obtain pain medications easily, and their persistence in pursuing accurate diagnoses and treatment. A major limitation of this study was that it relied on self-report and there were no urine drug screens to report."

Proske U, Gandevia SC. 2012. The proprioceptive senses: their roles in signaling body shape, body position and movement, and muscle force. Physiol Rev. 92(4):1651-1697. Proprioceptive senses "...include the senses of position and movement of our limbs and trunk, the sense of effort, the sense of force, and the sense of heaviness. Receptors involved in proprioception are located in skin, muscles, and joints. Information about limb position and movement is not generated by individual receptors, but by populations of afferents. Afferent signals generated during a movement are processed to code for endpoint position of a limb. The afferent input is referred to a central body map to determine the location of the limbs in space. Experimental phantom limbs, produced by blocking peripheral nerves, have shown that motor areas in the brain are able to generate conscious sensations of limb displacement and movement in the absence of any sensory input. In the normal limb tendon organs and possibly also muscle spindles contribute to the senses of force and heaviness. Exercise can disturb proprioception, and this has implications for musculoskeletal injuries. Proprioceptive senses, particularly of limb position and movement, deteriorate with age and are associated with an increased risk of falls in the elderly. [Trigger points can cause proprioceptive dysfunction, so this information is very important. DJS]

Provan SA, Austad C, Halsaa V et al. 2019. Fibromyalgia in patients with rheumatoid arthritis. A 10-year follow-up study, results from the Oslo Rheumatoid Arthritis Register. Clin Exp Rheumatol. [Jan 8 Epub ahead of print] In this study from FInland: "RA-FM was associated with significantly higher levels of cross-sectional and longitudinal RA disease activity. FM should be considered in patients with RA not reaching remission." [FM is a result and not a cause. It is to be considered in any chronic pain patient, as the central sensitization will amplify pain from any cause. It is therefore critical to identify and treat all of the irritants to the CNS. DJS]

Provan SA, Dean LE, Jones GT et al. 2021. The changing states of fibromyalgia in patients with axial spondyloarthritis: results from BSRBR-AS. Rheumatology (Oxford). Jan 6; Online ahead of print. "The presence of co-morbid FM should be considered in patients with persistent high axSpA disease activity and wide spread pain."

Pryma J. 2017. "Even my sister says I'm acting like a crazy to get a check": Race, gender, and moral boundary-work in women's claims of disabling chronic pain. Soc Sci Med. 181:66-73. "Recent research examines how women claim chronic pain in response to gendered moral discourses. However, extant research does not explore how race shapes the moral boundary-work performed by women suffering from disabling chronic pain. Through the qualitative analysis of twenty-four semi-structured interviews with women fibromyalgia sufferers conducted between October 2014 and August 2016 in the U.S.A., I demonstrate how women with fibromyalgia claim chronic pain by doing moral boundary-work, referencing gendered and racialized moral discourses that structure how claims of chronic pain as disability are and are not read as legitimate by doctors, disability bureaucrats and personal networks. Extending Hansen et al's work on stigma and the "pathologization of poverty," I suggest that, per my sample, the different moral discourses deployed in white and Black women's claims of chronic pain can be explained by the racialized and gendered boundaries of citizenship that structure U.S. welfare and disability politics. Finally, I argue for intersectionality's relevance to research on moral boundary-work and the medicalization of poverty."

Przekop P, Haviland MG, Zhao Y et al. 2012. Self-reported physical health, mental health, and comorbid diseases among women with irritable bowel syndrome, fibromyalgia, or both compared with healthy control respondents. J Am Osteopath Assoc. 112(11):726-735. "Physicians often encounter patients with functional pain disorders such as irritable bowel syndrome (IBS), fibromyalgia (FM), and their co-occurrence.... Respondents with IBS reported fewer traumatic and major life stressors and better health (ratings and comorbidity data) than respondents with FM or respondents with IBS plus FM. Overall, respondents with both diseases reported the worst stressors and physical-mental health profiles and reported more diagnosed medical, pain, and psychiatric comorbidities....The results revealed statistically significant, relatively large differences in perceptions of quality of life measures and health profiles among the respondents in the control group and the 3 clinical groups."

Przybylowicz PK, Sokolowska KE, Rola H, et al. DNA methylation changes in blood cells of fibromyalgia and chronic fatigue syndrome patients. J Pain Res. 2023 Nov 30:16:4025-4036. Methylomes of the blood cells of patients with FM and CFS in three independent studies have shown methylation changes that appear to be implicated in the pathogenesis of these syndromes.

Pujol J, Macia D, Garcia-Fontanals. 2014. The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia. Pain. [May 2 Epub ahead of print.] "The results confirm previous research demonstrating abnormal functional connectivity in fibromyalgia and show that alterations at different levels of sensory processing may contribute to account for clinical pain. Importantly, reduced functional connectivity extended beyond the somatosensory domain and implicated visual and auditory sensory modalities. Overall, this study suggests that a general weakening of sensory integration underlies clinical pain in fibromyalgia."

Pujol J, Martínez-Vilavella G, Llorente-Onaindia J et al. 2017. Brain imaging of pain sensitization in patients with knee osteoarthritis. Pain. [Jul 3 Epub ahead of print.] "We used functional magnetic resonance imaging (fMRI) to study pain sensitization in patients with knee osteoarthritis…. Results confirm the high prevalence of pain sensitization secondary to knee osteoarthritis. Relevantly, the sensitization phenomenon was associated with neural changes extending beyond strict pain-processing regions with enhancement of activity in general sensory, nonnociceptive brain areas. This effect is in contrast to the changes previously identified in primary pain sensitization in fibromyalgia patients presenting with a weakening of the general sensory integration."

Punjabi NM, Shahar E, Redline S et al. 2004.  Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study.  Am J Epidemiol. 160(6):521-530.  “Sleep-related hypoxemia was also associated with glucose intolerance independently of age, gender, body mass and waist circumference.  The results of this study suggest that SDB is independently associated with glucose intolerance and insulin resistance and lead to type 2 diabetes mellitus.”

Puretic MB, Demarin V. 2012. Neuroplasticity mechanisms in the pathophysiology of chronic pain. Clin Croat. 51(3):425-429. "Chronic pain is a widespread healthcare problem with great impact on mental health, professional and family life of the patient. It can be a consequence of many disorders; however, its pathogenesis has not yet been fully understood. Neuroplasticity is the ability of the nervous system to adapt to different changes and it is present throughout life, not only in prenatal period, infancy and childhood. However, in the pathophysiology of chronic pain, neuroplasticity shows its 'dark side'. Due to the central sensitization process, noxious stimuli can produce chronic pain or misinterpretation of non-noxious stimuli (secondary hyperalgesia and allodynia). These changes occur at the level of brain cortex as well at peripheral nerves and receptors. This review summarizes a significant portion of literature dealing with neuroplasticity processes in well known chronic pain conditions such as migraine, chronic posttraumatic headache, low back pain, fibromyalgia, and others." [This review from Croatia is well-thought-out and well-done. It is to be hoped that in the future, these researchers will include papers dealing with central sensitization generating TrPs in their research. DJS]

Puri BK, Lee GS, Schwarzbach A. 2021. Is fibromyalgia associated with borrelia specific T lymphocytes? Curr Rheumatol Rev. Sep 24. Online ahead of print. "It has recently been suggested that fibromyalgia symptomatology represents a T lymphocyte-mediated immune response to pathogens which are known risk factors for autoimmune diseases.… This novel controlled study provides no evidence of an association between fibromyalgia and Borrelia-specific T lymphocytes."

Qian S, Wang Y, Zhang X. 2019. Inhibiting histamine signaling ameliorates vertigo induced by sleep deprivation. J Mol Neurosci. [Jan 15 Epub ahead of print] "Although histamine inhibitors have been used in the motility-associated vertigo, the link between histamine and sleep deprivation (SD)-induced vertigo has not been clearly demonstrated. … . Histamine signaling inhibition may ameliorate SD-induced vertigo, and histamine can be considered as a potential treatment target." [Many things can cause vertigo, and this team from China found that sleep deprivation, at least in mice, is one of them, and they could ease it by inhibiting histamine signaling.]

Qin QG, Fu Y, Shi J et al. 2020. [Myofascial trigger point: an indicator of acupoint sensitization]. Zhen Ci Yan Jiu. 45(1):57-61. [Article in Chinese] "The primary pain areas or spots of the knee injury mainly distribute around the joint, whereas those of each muscle group lesion are often located in their respective skeletal muscle. Most of the referred pain areas often occur in the distal end of skeletal muscle and around the knee joint. Primary myofascial trigger points may be considered to be an indicator of acupoint sensitization."

Qu P, Yu JX, Chen GH. 2021. Neuroendocrine modulation of cognitive performance in the patients with fibromyalgia. Eur Neurol. May 11;1-11. "Forty-six patients with FM were compared with twenty-nine healthy controls (HCs)…. The FM patients had worse performance in attention, short-term memory, orientation, object working memory and spatial reference memory, higher depression scores, and worse sleep quality than HCs. The raised level of cortisol and gonadotropin-releasing hormone (GnRH) can protect general cognition, whereas the raised level of cortisol and thyroid-stimulating hormone (TSH) will damage spatial memory. Limitations: We did not study the sex hormones comprehensively. Conclusions: The FM patients showed significant cognitive impairment in several domains. The altered levels of cortisol, thyrotrophin-releasing hormone (TRH), and GnRH may mediate cognitive changes in FM."

Queiroz LP. 2013. Worldwide epidemiology of fibromyalgia. Curr Pain Headache Rep. 17(8):356. "This article reviews the prevalence and incidence studies done in the general population, in several countries/continents, the prevalence of FM in special groups/settings, the association of FM with some sociodemographic characteristics of the population, and the comorbidity of FM with others' disorders, especially with headaches."

Queiroz LB, Lourenco B, Silva LEV et al. 2017. Musculoskeletal pain and musculoskeletal syndromes in adolescents are related to electronic devices. J Pediatr (Rio J). [Nov 21 Epub ahead of print] "A cross-sectional study was performed in 299 healthy adolescents of a private school. All students completed a self-administered questionnaire, including: demographic data, physical activities, musculoskeletal pain symptoms, and use of simultaneous television/electronic devices (computer, internet, electronic games, and cell phones). Seven musculoskeletal pain syndromes were also evaluated: juvenile fibromyalgia, benign joint hypermobility syndrome, myofascial syndrome, tendinitis, bursitis, epicondylitis, and complex regional pain syndrome....A high prevalence of musculoskeletal pain/syndromes was observed in female adolescents. Musculoskeletal pain was mostly reported at a median age of 15 years, and students used at least two electronic devices. Reduced use of electronic games was associated with musculoskeletal pain syndromes. Free Article

Quek SY, Subramanian G, Patel J et al. 2015. Efficacy of regional nerve block in management of myofascial pain of masseteric origin. Cranio. [Dec 29 Epub ahead of print.] "MNB (masseteric nerve block) provided an immediate and sustained therapeutic effect for the management of myofascial pain for at least up to two weeks. MNB is a simple and valuable tool in the management of myogenous (muscle caused) pain, especially for the non-orofacial pain practitioner."

Quek SYP, Gomes-Zagury J, Subramanian G.2020. Twin block in myogenous orofacial pain: Applied anatomy, technique update, and safety. Anesth Prog. Jun 1;67(2):103-106. "Similar to the masseteric nerve block, the twin block has demonstrated efficacy with expeditious and sustained relief of myogenous face pain originating from the masseter muscle. Furthermore, in a 6-month prospective treatment study, that has been accepted for publication, the twin block has been demonstrated as comparable to trigger point injections in the management of chronic myofascial pain of masseteric origin. The twin block's ability to mitigate myogenous pain from both the masseter and temporalis muscles and its ease of administration are the key advantages over the masseteric nerve block…. This review describes the refined technique and its safety in the context of the region's applied anatomy".

Queme F, Taguchi T, Mizumura K et al. 2013. Muscular Heat and Mechanical Pain Sensitivity After Lengthening Contractions in Humans and Animals. J Pain. [Sep 21 Epub ahead of print]. "Mechanical sensitivity of muscle nociceptors was previously shown to increase 2 days after lengthening contractions (LC), but heat sensitivity was not different despite nerve growth factor (NGF) being upregulated in the muscle during delayed-onset muscle soreness (DOMS). The discrepancy of these results and lack of other reports drove us to assess the heat sensitivity during DOMS in humans and to evaluate the effect of NGF on the heat response of muscle C-fibers. Pressure pain thresholds and pain intensity scores to intramuscular injection of isotonic saline at 48°C and capsaicin were recorded in humans after inducing DOMS. The response of single unmyelinated afferents to mechanical and heat stimulations applied to their receptive field was recorded from muscle-nerve preparations in vitro. In humans, pressure pain thresholds were reduced but heat and capsaicin pain responses were not increased during DOMS. In rats, the mechanical but not the heat sensitivity of muscle C-fibers was increased in the LC group. NGF applied to the receptive field facilitated the heat sensitivity relative to the control. The absence of facilitated heat sensitivity after LC, despite the NGF sensitization, may be explained if the NGF concentration produced after LC is not sufficient to sensitize nociceptor response to heat….This article presents new findings on the basic mechanisms underlying hyperalgesia during DOMS, which is a useful model to study myofascial pain syndrome, and the role of NGF on muscular nociception. This might be useful in the search for new pharmacologic targets and therapeutic approaches."

Quraishi SA, Davies MJ, Craig TJ. 2004. Inflammatory responses in allergic rhinitis: traditional approaches and novel treatment strategies. J Am Osteopath Assoc. 104(5 Suppl 5):S7-S15. "Allergic rhinitis is associated with decreased learning, performance and productivity at work and school, as well as reduced quality of life. It's impact is estimated at 6-8 billion dollars, affecting 20% of adults and up to 40% of children. New strategies are continuing to develop to treat this condition.

Rachlin, E. S. ed. 1994. Myofascial Pain and Fibromyalgia Trigger Point Management Mosby: St. Louis.

Racine M, Castarlenas E, de la Vega R et al. 2014. Sex differences in psychological response to pain in patients with fibromyalgia syndrome. Clin J Pain. Oct 17. [Epub ahead of print] "For pain-related beliefs, men were more likely to view pain as reflecting harm, and they were also more likely than women to use activity avoidance as a pain coping strategy…. The study findings suggest that women and men with FMS may think about and cope with pain somewhat differently, and may therefore benefit from different types of psychosocial pain intervention."

Racine M, Sanchez-Rodríguez E, de la Vega R et al. 2019. Pain-related activity management patterns as predictors of treatment outcomes in patients with fibromyalgia syndrome. Pain Med. [Oct 18 Epub ahead of print] "Outcomes were assessed at pre- and post-treatment, and patients provided demographic information and completed measures assessing pain intensity, pain interference, psychological function, physical function, and pain management activity patterns. Three linear hierarchical regression analyses predicting changes in pain outcomes from changes in pacing, overdoing, and avoidant activity patterns were performed…. Changes in pain-related activity patterns made significant contributions to the prediction of changes in patients' function. Specifically: (a) increases in overdoing predicted reductions in pain interference; (b) decreases in avoidance predicted improvements in psychological function; and (c) increases in pacing predicted improvements in physical function…. This study provides support for a role of activity management treatments in improved adjustment to chronic pain."

Radanov BP, Sturzenegger M, Di Stefano G. 1995.  Long-term outcome after whiplash injury.  A 2-year follow-up considering features of injury mechanism and somatic, radiologic, and psychosocial findings.  Medicine 74(5):281-297.  “Symptomatic patients were older, had higher incidence of rotated or inclined head position at the time of impact, had higher prevalence of pretraumatic headache, showed higher intensity of initial neck pain and headache, complained of a greater number of symptoms, had a higher incidence of symptoms of radicular deficit and higher average scores on a multiple symptom analysis, and displayed more degenerative signs on X-ray.  Symptomatic patients scored higher with regard to impaired well-being and performed worse on tasks of attentional functioning and showed more concern with regard to long-term suffering and disability.”

Radi R, Huang H, Rivera J, et al. Is low-dose naltrexone effective in chronic pain management? J Fam Pract. 2023 Sep;72(7):320-321. YES. Low-dose naltrexone is as effective as amitriptyline in the treatment of painful diabetic neuropathy and has a superior safety profile (strength of recommendation [SOR], B; single randomized controlled trial [RCT]). Low-dose naltrexone significantly reduced pain by 32% in inflammatory conditions and 44% in neuropathic conditions (SOR, B; single retrospective cohort study). Doses as low as 5.4 mg were found to reduce pain in 95% of patients with fibromyalgia (SOR, B; single prospective dose-response study).

Raeissadat SA, Rayegani SM, Sadeghi F et al. 2018. Comparison of ozone and lidocaine injection efficacy vs dry needling in myofascial pain syndrome patients. J Pain Res. 29;11:1273-1279. "Myofascial pain syndrome (MPS) is a common musculoskeletal disorder among young adults associated with presence of myofascial trigger points. We aimed to evaluate efficacy of ozone injection (OI) in MPS patients, compared with two currently used methods including lidocaine injection (LI) and dry needling (DN).... In summary, this data showed that in short-term follow-up, all three methods were significantly effective in MPS treatment; however, OI and LI groups had slightly better results than the DN group, with no remarkable preference between them."

Ragab A, Clement P, Vincken W. 2004.  Objective assessment of lower airway involvement in chronic rhinosinusitis.  Am J Rhinol. 18(1):15-21.  Sixty percent of chronic rhinosinusitis patients have lower airway involvement, 24 % had asthma and 36% had small airway disease.  These may often be unsuspected.

Raghavendra V, Tanga FY, DeLeo JA. 2004.  Attenuation of morphine tolerance, withdrawal-induced hyperalgesia, and associated spinal inflammatory immune responses by propentofylline in rats.  Neuropsychopharmacology 29(2):327-334.  This study indicates that propentopylline, a glial cell modulator and anti-inflammatory agent, can restore the analgesic efficacy of morpihine.  “These results further support the hypothesis that spinal glia and proinflammatory cytokines contribute to the mechanisms of morphine tolerance and associated abnormal pain sensitivity.”

Rahman MS, Winsvold BS, Chavez Chavez SO, et al. 2021. Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain. Ann Rheum Dis. Published online ahead of print April 29. "Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%-54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP…. We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis."

Rahman W, Dickenson AH. 2013. Voltage gated sodium and calcium channel blockers for the treatment of chronic inflammatory pain. Neurosci Lett. [Aug 11 Epub ahead of print]. "The inflammatory response is a natural response of the body that occurs immediately following tissue damage, which may be due to injury, infection or disease. The acute inflammatory response is an essential mechanism that promotes healing and a key aspect is the ensuing pain, which warns the subject to protect the site of injury. Thus, it is common to see a zone of primary sensitization as well as consequential central sensitization that generally, is maintained by a peripheral drive from the zone of tissue injury. Inflammation associated with chronic pain states, such as rheumatoid and osteoarthritis, cancer and migraine etc. is deleterious to health and often debilitating for the patient. Thus there is a large unmet clinical need. The mechanisms underlying both acute and chronic inflammatory pain are extensive and complex, involving a diversity of cell types, receptors and proteins. Among these the contribution of voltage gated sodium and calcium channels on peripheral nociceptors is critical for nociceptive transmission beyond the peripheral transducers and changes in their distribution, accumulation, clustering and functional activities have been linked to both inflammatory and neuropathic pain. The latter has been the main area for trials and use of drugs that modulate ion channels such as carbamazepine and gabapentin, but given the large peripheral drive that follows tissue damage, there is a clear rationale for blocking voltage gated sodium and calcium channels in these pain states. It has been hypothesized that pain of inflammatory origin may evolve into a condition that resembles neuropathic pain, but mixed pains such as low back pain and cancer pain often include elements of both pain states. This review considers the therapeutic potential for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states." [This paper confirms the role of peripheral pain generation in initiating the central sensitization state. It is very interesting, considering the idea that trigger points may be associated with a calcium channelopathy. DJS]

Rahn EJ, Guzman-Karlsson MC, David Sweatt J. 2013. Cellular, molecular, and epigenetic mechanisms in non-associative conditioning: Implications for pain and memory. Neurobiol Learn Mem. [Jun 22 Epub ahead of print]. "Sensitization is a form of non-associative conditioning in which amplification of behavioral responses can occur following presentation of an aversive or noxious stimulus. Understanding the cellular and molecular underpinnings of sensitization has been an overarching theme spanning the field of learning and memory as well as that of pain research. In this review we examine how sensitization, both in the context of learning as well as pain processing, shares evolutionarily conserved behavioral, cellular/synaptic, and epigenetic mechanisms across phyla. First, we characterize the behavioral phenomenon of sensitization both in invertebrates and vertebrates. Particular emphasis is placed on long-term sensitization (LTS) of withdrawal reflexes in Aplysia following aversive stimulation or injury, although additional invertebrate models are also covered. In the context of vertebrates, sensitization of mammalian hyperarousal in a model of post-traumatic stress disorder (PTSD), as well as mammalian models of inflammatory and neuropathic pain is characterized. Second, we investigate the cellular and synaptic mechanisms underlying these behaviors. We focus our discussion on serotonin-mediated long-term facilitation (LTF) and axotomy-mediated long-term hyperexcitability (LTH) in reduced Aplysia systems, as well as mammalian spinal plasticity mechanisms of central sensitization. Third, we explore recent evidence implicating epigenetic mechanisms in learning- and pain-related sensitization. This review illustrates the fundamental and functional overlay of the learning and memory field with the pain field which argues for homologous persistent plasticity mechanisms in response to sensitizing stimuli or injury across phyla."

Rainey CE. 2013. The use of trigger point dry needling and intramuscular electrical stimulation for a subject with chronic low back pain: a case report. Int J Sports Phys Ther 8(2):145-161. The subject of this case report is a 30 year old female on active military duty, who developed low back and right posteriolateral hip pain after a lumbar flexion injury from picking up a barbell. Exam revealed a multi-segmental flexion movement pattern dysfunction, with TrPs in the right gluteus maximus and medius. Dry needling of the trigger points and intramuscular stimulation coupled with a home program of core stability exercises helped the patient return to full military duty without pain.

Rainville P, Bushnell MC, Duncan GH. 2001.  Representation of acute and persistent pain in the human CNS: potential implications for chemical intolerance.  Ann N Y Acad Sci. 933:130-141.  CNS neuroplasticity involved in chronic pain may share similarities with environmental chemical sensitivity.

Raison CL, Capuron L, Miller AH. 2005.  Cytokines sing the blues: inflammation and the pathogenesis of depression.  Trends Immunol. [Nov 26 Epub ahead of print]  “Depression might be a behavioral byproduct of early adaptive advantages conferred by genes that promote inflammation.  These findings suggest that targeting proinflammatory cytokines and their signaling pathways might represent a novel strategy to treat depression.”  [This may be a helpful treatment strategy for patients with both depression and FMS. DJS]

Raja G P, Fernandes S, Cruz AM et al. 2020. The plausible role of deep cervical fascia and its continuum in chronic craniofacial and cervicobrachial pain: A case report. Heliyon. Jul 27;6(7):e04560. "This case report highlights the possible role of dysfunction of the DCF (deep cervical fascia) and the importance of assessing myofascial chains in patients with pain in the UQR (upper quarter region). The report has also shown that FM (fascial manipulation) may be beneficial and can be considered an adjunct in the rehabilitation of chronic CFP (craniofacial pain) and CBP (cervicobrachial pain). Nevertheless, future studies with multiple sessions and follow-ups are imperative."

Rakovski C, Zettel-Watson L, Rutledge D. 2012. Association of employment and working conditions with physical and mental health symptoms for people with fibromyalgia. Disabil Rehabil. [Feb 12 Epub ahead of print]. "Work modifications could allow more people with FM to remain employed and alleviate symptoms. Persons with FM should be counseled to consider what elements of their work may lead to symptom exacerbation." [To do these modifications adequately, one must take into consideration the peripheral pain generators that are causing and/or maintaining the central sensitization of FM. Controlling the perpetuating factors of the peripheral pain generators can substantially help in the management of FM. DJS]

Raloff, J. 2000. More Waters Test Positive for Drugs. Sci News157(14):212.

Ramanathan S, Panksepp J, Johnson B. 2012. Is Fibromyalgia An Endocrine/Endorphin Deficit Disorder? Is Low Dose Naltrexone a New Treatment Option? Psychosomatics. [Apr 3 Epub ahead of print].

Ramirez M, Martínez-Martínez LA, Hernandez-Quintela E et al. 2015. Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy. Semin Arthritis Rheum. [Mar 19 Epub ahead of print.] "A consistent line of investigation suggests that fibromyalgia is a neuropathic pain syndrome. This outlook has been recently reinforced by several controlled studies that describe decreased small nerve fiber density in skin biopsies of patients with fibromyalgia. The cornea receives the densest small fiber innervation of the body." This study revealed that: "Women suffering from fibromyalgia have thinner corneal stromal nerves and diminished sub-basal plexus nerve density when compared to healthy controls … Corneal confocal microscopy could become a useful test in the study of patients with fibromyalgia."

Ramirez-Tejero JA, Martinez-Lara E, Rus A et al. 2018. Insight into the biological pathways underlying fibromyalgia by a proteomic approach. J Proteomics. [Jul 17 Epub ahead of print] "We found a total of 33 proteins differentially expressed in patients with FM. Haptoglobin and fibrinogen showed the highest FM/control ratio.... Our data demonstrate the existence of a common protein signature in the plasma of patients with FM that could explain some of the symptoms associated to this syndrome. The analysis of the 33 proteins differentially expressed corroborates the crucial role of inflammation in the pathogenesis of this syndrome. The interplay of the complement and coagulation cascades contributes to the inflammatory process, while the activation of Liver-X Receptor/Retinoid-X Receptor and Farnesoid-X Receptor/Retinoid-X Receptor could attempt to alleviate it. Finally, we have identified two proteins, haptoglobin and fibrinogen, as potential biomarker-candidates of FM for future studies."

Ramon S, Espanol A, Yebra M, et al. 2021. [Current evidences in shockwave treatment. SETOC (Spanish Society of Shockwave Treatment) recommendations] Rehabilitacion (Madr). Mar 17;S0048-7120(21)00026-8. [Spanish] "This SETOC consensus document shows the scientific evidence of the technology in shockwaves (SW) and radial pressure waves (RPW) in a variety of spasticity disorders, musculoskeletal, skin, urological diseases, etc. SW and RPW, without anesthesia, are an effective, safe, non-invasive, cost-effective treatment, which reduces the need for surgery, lower risk of complications, faster recovery and greater acceptability to patients than surgery. Consequently, SW and RPW should be the first therapeutic option in the aforementioned chronic pathologies, when conservative alternatives have failed."

Ramon S, Gleitz M, Hernandez L et al. 2015. Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia. Int J Surg. [Sept 10. Epub ahead of print.] "Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM)."

Rangon FB, Koga Ferreira VT, Rezende MS et al. 2018. Ischemic compression and kinesiotherapy on chronic myofascial pain in breast cancer survivors. J Bodyw Mov Ther. 22(1):69-75. "Ischemic compression associated with kinesiotherapy increases the pressure pain threshold on the myofascial trigger point in the upper trapezius muscle and reduces the intensity of pain in breast cancer survivors with myofascial pain." [Breast cancer survivors often have trigger points. This study shows that the trapezius trigger points are often part of the pain generators. Other affected muscles, such as the pectoralis muscles, as well as scar tissue, should also be checked for trigger points. DJS]

Ranker A, Wegener B, Winkelmann A et al. 2019. [Undetected coccyx fracture in a woman with fibromyalgia]. Schmerz. [Jul 8 Epub ahead of print] [Article in German] "This article presents the case of a 46-year-old woman with fibromyalgia with an undetected fracture of the coccyx. The heterogeneity of the symptoms of patients suffering from fibromyalgia including chronic widespread pain, vegetative and functional disorders, mental and physical exhaustion as well as sleep disorders can cause accidentally undetected comorbidities, especially if these are rare and predominantly present with pain as the main symptom. In the present case the reason for symptoms was detected only after 14 months of ineffective therapies and diagnostic procedures. The coccygeal pain was eliminated through a coccygectomy as ultima ratio. It should be nevertheless emphasized that patients with fibromyalgia suffer from a central pain-processing disorder. Indications for operative treatment must be very carefully considered. Surgery should only be considered in consultation with the patient and after failed conservative therapy."

Ransone JW, Schmidt J, Crawford SK et al. Effect of manual compressive therapy on latent myofascial trigger point pressure pain thresholds. Bodyw Mov Ther. 2019 Oct;23(4):792-798. "PPT (pressure pain threshold) continued to increase after several weeks of MCT (manual compressive therapy) when applied directly on or within 2.5 cm of an identified LTP (latent myofascial trigger point) compared to control." [Compression should not last long enough to deprive the TrP area of blood flow. DJS]

Ranum RM, Toussaint LL, Whipple MO, et al. 2022. Predictive bidirectional relations between pain, fatigue, and dyscognition in fibromyalgia. Mayo Clin Proc Innov Qual Outcomes. Feb 21;6(2):143-147. Pain seen at the beginning of the study predicted later pain, cognitive dysfunction, and fatigue. Fatigue seen at the beginning was associated only with later fatigue. Cognitive dysfunction seen at the beginning was predictive of later pain and fatigue.

Rao SG. 2002.  The neuropharmacology of centrally-acting analgesic medications in fibromyalgia.  Rheum Dis Clin North Am 28(2):235-259.  “FMS consists of more than just chronic pain, and the question of how sleep abnormalities, depression, fatigues, and so forth tie into disordered pain processing is being researched actively.  Future research focusing on how the various manifestations of FMS related to one another undoubtedly will lead to a more rational targeting of drugs in this complex disorder.”

Raouf R, Quick K, Wood JN. 2010. Pain as a channelopathy. J Clin Invest. 120(11):3745-3752. "Mendelian heritable pain disorders have provided insights into human pain mechanisms and suggested new analgesic drug targets. Interestingly, many of the heritable monogenic pain disorders have been mapped to mutations in genes encoding ion channels. Studies in transgenic mice have also implicated many ion channels in damage sensing and pain modulation. It seems likely that aberrant peripheral or central ion channel activity underlies or initiates many pathological pain conditions. Understanding the mechanistic basis of ion channel malfunction in terms of trafficking, localization, biophysics, and consequences for neurotransmission is a potential route to new pain therapies." [This is interesting in that the most likely current hypothesis for the cause of myofascial TrPs is a calcium channelopathy. DJS]

Raphael KG, Janal MN, Nayak S et al. 2006.  Psychiatric comorbidities in a community sample of women with fibromyalgia.  Pain [May 12 Epub ahead of print]  “Prior studies of care-seeking fibromyalgia (FM) patients often report that they have an elevated risk of psychiatric disorders, but biased sampling may distort true risk.”  “Although risk of current MDD was nearly 3-fold higher in community women with than without FM, the groups had similar risk of lifetime MDD.  Risk of lifetime anxiety disorders, particularly obsessive compulsive disorder and post-traumatic stress disorder, was approximately 5-fold higher among women with FM.  Overall, this study found a community prevalence for FM among women that replicates prior North American studies and revealed that FM may be even more prevalent among racial minority women.  These community-based data also indicate that the relationship between MDD and FM may be more complicated than previously thought, and call for an increased focus on anxiety disorders in FM.”

Rappold T, Suleman MI. 2019. Functional abdominal pain in a pediatric patient after resolution of acute pancreatitis: A case report. A A Pract. [Feb 21 Epub ahead of print] "Children with acute pancreatitis may develop chronic abdominal wall pain after resolution of clinical, laboratory, and radiographic signs of disease. We describe a 13-year-old boy who underwent an unrevealing, complex diagnostic evaluation for persistent abdominal pain after resolution of acute pancreatitis. His pain required an extended leave of absence from school and nasogastric tube feeds. After receiving abdominal nerve blocks and trigger point injections, he experienced near-complete resolution of pain with normalization of eating habits and daily function." [How much misery caused and resources wasted because medical care providers are untrained in myofascial medicine? DJS]

Rasmussen, D. D., B. M. Boldt, C. W. Wilkinson, S. M. Yellon and A. M. Matsumoto. 1999.Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology 140(2):1009-12.

Rauck R, Busch M, Marriott T. 2013. Effectiveness of a heated lidocaine/tetracaine topical patch for pain associated with myofascial trigger points: results of an open-label pilot study. Pain Pract. 13(7):533-538. This study was done on patients with up to three myofascial trigger points. They found that: "The heated lidocaine/tetracaine patch has potential utility as a noninvasive pharmacologic approach for managing MTP pain. Further studies are warranted." [For those of us with hundreds of trigger points, this still might be useful for the worst TrPs. Please do not try this at home. The patches were designed to release the topical anesthetic slowly. As of now, the patches contain warnings not to use them with heat, as a much higher amount of lidocaine could enter the body much more rapidly, and could have systemic effects on blood pressure and other systems. DJS]

Rayegani S, Bahrami M, Samadi B et al. 2011. Comparison of the effects of low energy laser and ultrasound in treatment of shoulder myofascial pain syndrome: a randomized single-blinded clinical trial. Eur J Phys Rehabil Med. 47(3):381-389. "Myofascial pain syndrome (MPS) is one of the most prevalent musculoskeletal diseases. MPS impaired quality of life in the patients. There is a lot of controversy about different treatment options which include medical treatments, physical therapy, injections, ultrasound and laser.... This study introduces laser as one of the preferred treatments of myofascial pain syndrome in shoulder." [It is a sad commentary on the state of medical care that most care providers are unaware that this common cause of musculoskeletal pain even exists. DJS]

Rayhan RU, Ravindran MK, Baraniuk JN. 2013. Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation. Front Physiol. 4:181. "The high prevalence of migraine in CFS (chronic fatigue syndrome) was confirmed and extended to GWI (gulf war illness) subjects. GWI and CFS may share dysfunctional central pathophysiological pathways that contribute to migraine and subjective symptoms. The high migraine prevalence warrants the inclusion of a structured headache evaluation in GWI and CFS subjects, and treatment when present."

Rea, T., J. Russo, W. Katon, R. L. Ashley and D. Buchwald. 1999. A prospective study of tender points and fibromyalgia during and after an acute viral infection. Arch Intern Med159(8):865-707.

Ready LB, Kozody R, Barsa JE et al. 1983.  Trigger point injections vs. jet injection in the treatment of myofascial pain.  Pain. 15(2):201-206.  “Trigger point injections using dilute solutions of local anesthetic agents have proved effective for many patients with myofascial pain.  The treatment itself, however, can produce severe pain and may occasionally be associated with complications.  It was determined in this study that a local anesthetic solution administered by jet injection in the area of myofascial trigger points was capable of providing short-term pain relief equal to conventional trigger point injections using a hypodermic needle and syringe.  The jet injector system produced significantly less pain during treatment than conventional trigger point injections and therefore was preferred by most subjects having the opportunity to compare both forms of treatment.”

Reddy RS, Tedla JS, Dixit S et al. 2019. Cervical proprioception and its relationship with neck pain intensity in subjects with cervical spondylosis. BMC Musculoskelet Disord. Oct 15;20(1):447. "Proprioception is impaired in subjects with CS (cervical spondylosis) when compared to healthy control group. Higher pain intensity was associated with greater cervical JPE (joint position error) in patients with CS."

Redondo JR, Justo CM, Moraleda FV et al. 2004.  Long-term efficacy of therapy in patients with fibromyalgia: A physical exercise-based program and a cognitive-behavioral approach. Arthritis Rheum 51(2):184-192.  This study showed that “improvement in self-efficacy and physical fitness are not associated with improvement in clinical manifestations.”

Redwine L, Hauger RL, Gilin JC et al. 2000.  Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans.  J Clin Endocrinol Metab 85(10:3597-3603.  There is an association between sleep stages and IL-6 levels.  Populations with increased REM and relative loss of deep sleep [some FMS patients may fall in this category.  DJS] have elevated nighttime concentrations of IL-6.  This may signify increased inflammatory disease risk.  [It also may be a cause for chronic pain – see Focus on Pain 2003.  DJS]

Reece PH, Wyatt M, O’Flynn P. 1999.  Dercum’s disease (adiposis dolorosa).  J Laryngol Otol. 113(2):174-176.  Dercum’s disease, also called lipomtosis dolorosa and a variety of other names, is characterized by progressively painful fatty deposits.  There is at least 3 months pain in fatty deposits, and may be excessive fatigue, obesity, and mental disturbances including confusional states.  It is rare, but may be misdiagnosed as FM, or it may co-exist with FM and some of the confusional states and other symptoms may be due to co-existing conditions.  DJS]

Reed BD, Harlow SD, Plegue MA et al. 2016. Remission, relapse, and persistence of vulvodynia: A longitudinal population-based study. J Womens Health (Larchmt). [Jan 11 Epub ahead of print.] "Remission of vulvodynia symptoms is common with approximately half of remitters experiencing a relapse within 6-30 months. Persistence without remission is the exception rather than the rule. Pain history and comorbid conditions were associated with the more severe outcomes of relapse and/or persistence compared with those who remitted only. These findings provide further support that vulvodynia is heterogeneous and often occurs in an episodic pattern."

Reed BD, Harlow SD, Sen A et al. 2012. Relationship between vulvodynia and chronic comorbid pain conditions. Obstet Gynecol. 120(1):145-151. "To estimate the relationship among the presence of vulvodynia, fibromyalgia, interstitial cystitis, and irritable bowel syndrome. Validated questionnaire-based screening tests for the four pain conditions were completed by women with and without vulvodynia who were participating in the Michigan Woman to Woman Health Study, a longitudinal population-based survey in southeastern Michigan. Weighted population-based estimates of the prevalence and characteristics of participants with these chronic comorbid pain conditions were calculated using regression analyses....Chronic pain conditions are common, and a subgroup of women with vulvodynia is more likely than those without vulvodynia to have one or more of the three other chronic pain conditions evaluated. [It is most unfortunate that myofascial trigger points, one of the main co-existing conditions of vulvodynia as well as one of the main causes, was not included in this study. DJS]

Reeh ES, elDeeb ME. 1991. Referred pain of muscular origin resembling endodontic involvement. Case report. Oral Surg Oral Med Oral Pathol. 71(2):223-227. This case report discusses a patient with tooth pain caused by a myofascial trigger point.

Regunath H, Cochran K, Cornell K et al. 2016. Is it painful to manage chronic pain? A cross-sectional study of physicians-in-training in a university program. Mo Med. 113(1):72-78. "Prescribing opioids for chronic non-cancer pain (CNCP) is a challenge due to associated risks from abuse, addiction and adverse effects. We surveyed resident physicians on their knowledge, attitude and practices in opioid prescription practices in the ambulatory setting and conducted an educational module to address their knowledge gaps…. Internal medicine residents perceived deficits in their ability to manage CNCP. Following a focused educational training, residents' knowledge and confidence in prescription of opioids improved, demonstrating the need to include management of CNCP with opioids into their curriculum."

Rehm SE, Koroschetz J, Gockel U et al. 2010. A cross-sectional survey of 3035 patients with fibromyalgia: subgroups of patients with typical comorbidities and sensory symptom profiles. Rheumatology (Oxford). [Mar 17 Epub ahead of print]. “Patients with FM…present with a variety of pain qualities, sensory abnormalities and additional comorbidities. The aim was to identify clinically distinguishable subgroups of patients….Clinically relevant sensory abnormalities (strongly, very strongly present) included pressure pain (58%), prickling (33%), burning (30%) and thermal hypersensitivity (24%). Pain attacks were complained by 40% of patients. Moderate to severe comorbid depression occurred in 66% of patients. Only approximately 30% of the patients had optimal sleep. A hierarchical cluster analysis using descriptors of sensory abnormalities as well as the extent of comorbidities revealed five distinct subgroups of patients showing a characteristic clinical profile. Four subgroups of patients suffer from severe sensory disturbances in various combinations but lack pronounced comorbidities. In one subgroup, however, severe comorbidities dominate the clinical picture. ….The results of this study indicate that FM patients can be classified on the basis of their sensory symptoms and comorbidities by the use of a patient-reported questionnaire. Subgrouping of patients with FM may be used for future research and to tailor optimal treatment strategies for the appropriate patient.”

Reibel MD, Hutti MH. 2020. The role of helplessness in the appraisal of illness uncertainty in women with fibromyalgia. Nurs Sci Q. Oct;33(4):346-352. "Fibromyalgia is a chronic pain disorder characterized by uncertainty in etiology, symptomatology, diagnosis, treatment, and outcome. The high level of illness uncertainty that results from fibromyalgia is a risk factor for maladjustment to illness…. We found illness uncertainty is negatively associated with subjective well-being and that helplessness strongly influences the impact of illness uncertainty on subjective well-being in women with fibromyalgia". [The perception of helplessness may be what can cause negative impact. Once patients are shown that some symptoms are due to factors that can be addressed, the perception of helplessness may diminish. DJS]

Reich JW, Johnson LM, Zautra AJ et al. 2006.  Uncertainty of illness relationships with mental health and coping processes in fibromyalgia patients.  J Behav Med. [May 6 Epub ahead of print]   “Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain condition poorly understood in terms of etiology and treatment by both physicians and patients. This condition of ‘uncertainty of illness’ was examined as a variable involved in the adjustment of FMS patients, relating it to their depression, anxiety, affect and coping styles.”  “Both cross-sectional and more dynamic longitudinal analyses showed that illness uncertainty was significantly associated with anxiety, negative affect, and avoidant and passive coping. Its positive relationship with depression was eliminated when a control variable, pain helplessness, was included as a covariate. Longitudinally, illness uncertainty interacted with interpersonally stressful daily events in predicting reports of reduced positive affect, suggesting that illness uncertainty acts as a risk factor for affective disturbances during stressful times.” 

Reich JW, Olmsted ME, van Puymbroeck CM. 2006.  Illness uncertainty, partner caregiver burden and support, and relationship satisfaction in fibromyalgia and osteoarthritis patients.  Arthritis Rheum. 55(1):86-93.  “Partner caregiver burden was related to lower levels of partner supportiveness for the FMS dyads, but not for the OA dyads.”  “The results suggest that uncertainty of illness is a prominent feature affecting patients with FMS in their relationships with their partners.”

Reichling DB, Levine JD. 2009.  Critical role of nociceptors plasticity in chronic pain.  Trends Neurosci. [Sep 23 Epub ahead of print]  “The transition from acute to chronic pain states might be the most important challenge in research to improve clinical treatment of debilitating pain.  We describe a recently identified mechanism of neuronal plasticity in primary afferent nociceptive nerve fibers (nociceptors) by which an acute inflammatory insult or environmental stressor can trigger long-lasting hypersensitivity of nociceptors to inflammatory cytokines.  This phenomenon, ‘hyperalgesic priming’, depends on the epsilon isoform of protein kinase C (PKCvarepsilon) and a switch in intracellular signaling pathways that mediate cytokine-induced nociceptor hyperexcitability.  We discuss the impact of this discovery on our understanding of, and ultimately our ability to treat, a variety of enigmatic and debilitating pain conditions, including those associated with repetitive injury and generalized pain conditions, such as fibromyalgia.”

Reichmann H, Schaefer J. 2004.  Painful myopathies – metabolism of muscle cells and metabolic myopathies.  J Musculoskeletal Pain 12(3/4):75-83.   Types of myalgia considered in this article include causes of focal muscle pain such as restless leg syndrome and neurogenic pain, causes of diffuse muscle pain such as FMS, paroxysmal muscle pain such as contractures (which may be caused by TrPs) and exercise-induced muscle pain.  This excellent article on myopathies makes several points which are relevant to FMS or TrPs.  There is a clear and detailed explanation of energy metabolism in muscle mitochondria.  There is a clear explanation of muscle pain pathogenesis in myopathies.  Tissue pH importance, now found to be lowered at the TrP local twitch response (Shah et al 2005) is highlighted.   Muscle soreness caused by mechanical microrupture of the sarcomeric structures described in the article may happen in over-vigorous physical therapy, especially in patients with the combination of FMS and TrPs.  The article describes the hypersensitivity of FMS patients to normal mechanical stimuli.  A central nervous system disease may cause secondary myalgia due to spasticity or rigidity.  [Patients with chronic myofascial pain complex may have muscle tightness to the point of pain.]  Contractures are described briefly as never occurring at rest, but only after repetitive muscle contractions.  [Patients with chronic myofascial pain complex can have muscles in permanent contracture.  The muscles do not seem to be able to relax.  DJS] Disturbances in muscle metabolism can cause contractures, and among these are channelopathies.  [It has been proposed that myofascial TrPs are a type of channelopathy.  DJS] “All patients with a defect in glucose metabolism should have a protein-rich diet.”  Patients must learn to avoid overuse of their muscles, and “avoid endurance exercise with abnormalities of aerobic metabolism and to avoid brief intensive exercise with disturbances of anaerobic metabolism.”

Reidenberg, M. M. and R. K. Portenoy. 1994. The need for an open mind about the treatment of nonmalignant pain. Clin Pharmacol Ther 55(4):367-369.

Reiestad F, Kulkarni J. 2013. Role of myofascial trigger points in post-amputation pain: causation and management. Prosthet Orthot Int. 37(2):120-123. "Identification of myofascial trigger points in amputation stumps and their role in post-amputation pain, followed by appropriate intervention is an important facet of management of this complex chronic pain. Clinical relevance Myofascial trigger points in amputation stumps can lead to ongoing chronic post-amputation pain and our results indicate that identification and intervention of these trigger points does lead to notable resolution of this pain."

Reilich P, Fheodoroff K, Kern U et al. 2004.  Consensus statement: botulinum toxin in myofascial pain.  J Neurol 251(Suppl 1):1/36-1/38.  Botulinum toxin is suitable for patients with myofascial TrPs who have poor clinical outcomes after at least a month of physical therapy, including dry needling and medications.  Two techniques are explained.  It must be used with caution, and only as part of multimodal therapy.

Reis AM, Brito LGO, Teixeira CPF et al. 2021. Is there a difference in whole body standing posture in women with urinary incontinence based on the presence of myofascial dysfunction in the pelvic floor muscles? Phys Ther. Jul 6. Online ahead of print.... Women with UI and MD had greater anterior pelvic tilt and posterior displacement of the body than women without dysfunction.... During a postural screen, health care professionals should look for anterior pelvic tilt relative to horizon when evaluating posture in women with UI and MD. The findings of postural changes in women with MD and UI may influence the PFM assessment.... Women with involuntary urinary loss, pain, and stiffness in the pelvic area may show changes in posture associated with this condition.

Reisenauer SJ. 2012. A needle in the neck: trigger point injections as headache management in the emergency department. Adv Emerg Nurs J. 34(4):350-356. "A review of recent research suggests that the use of trigger point injections is successful in relieving the acute pain of musculoskeletal headaches. Patients with the chief complaint of headache commonly present to the emergency department (ED) and are often treated with multiple intravenous medications including narcotics....This article will address the problems of intravenous medication therapy and discuss the benefits of trigger point therapy as management for musculoskeletal headaches specifically in the ED. In addition, discussion aims to provide tools for the nurse practitioner to integrate this skill into clinical practice."

Ren K, Dubner R. 2008. Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 21(5):570-579. "Evidence indicates that central glial activation depends on nerve inputs from the site of injury and release of chemical mediators. Hematogenous immune cells may migrate to/infiltrate the brain and circulating inflammatory mediators may penetrate the blood-brain barrier to participate in central glial responses to injury. Inflammatory cytokines such as interleukin-1beta released from glia may facilitate pain transmission through its coupling to neuronal glutamate receptors. This bidirectional neuron-glia signaling plays a key role in glial activation, cytokine production and the initiation and maintenance of hyperalgesia. Recognition of the contribution of the mutual neuron-glia interactions to central sensitization and hyperalgesia prompts new treatment for chronic pain."

Renan-Ordine R, Alburquerque-Sendi N F, Rodrigues de Souza DP et al. 2011. Effectiveness of myofascial trigger point manual therapy combined with a self-stretching protocol for the management of plantar heel pain: a randomized controlled trial. J Orthop Sports Phys Ther. 41(2):43-50. A self-stretching program coupled with bodywork on TrPs was far superior to self-stretching alone in the relief of plantar heel pain.

Renaud KJ. 2015. Vestibular function and depersonalization/derealization symptoms. Multisens Res. 28(5-6):637-651."Patients with an acquired sensory dysfunction may experience symptoms of detachment from self or from the environment, which are related primarily to nonspecific symptoms of common mental disorders and secondarily, to the specific sensory dysfunction. This is consistent with the proposal that sensory dysfunction could provoke distress and a discrepancy between the multi-sensory frame given by experience and the actual perception. Both vestibular stimuli and vestibular dysfunction can underlie unreal experiences. Vestibular afferents provide a frame of reference (linear and angular head acceleration) within which spatial information from other senses is interpreted. This paper reviews evidence that symptoms of depersonalization/ derealization associated with vestibular dysfunction are a consequence of a sensory mismatch between disordered vestibular input and other sensory signals of orientation."

Reyes Del Paso GA, Contreras-Merino AM, de la Coba P et al. 2021. The cardiac, vasomotor, and myocardial branches of the baroreflex in fibromyalgia: Associations with pain, affective impairments, sleep problems, and fatigue. Psychophysiology Mar 1; Online ahead of print. "Reduced function of the three baroreflex branches implies diminished resources for autonomic inotropic, chronotropic, and vascular regulation in fibromyalgia. Blunted stress reactivity indicates a limited capacity for autonomic cardiovascular adjustment to situational requirements. The associations of BRS (baroreflex sensitivity) and BEI (baroreflex effectiveness) with pain perception may reflect the antinociceptive effects arising from baroreceptor afferents, where reduced baroreflex function may contribute to the hyperalgesia characterizing fibromyalgia. The associations with affective impairments, sleep problems, and fatigue suggest that baroreflex dysfunctions are also involved in the secondary symptoms of the disorder." [The carotid baroreflex could also be influenced by area TrPs. DJS]

Reyes Del Paso GA, Garrido S, Pulgar A et al. 2011. Autonomic cardiovascular control and responses to experimental pain stimulation in fibromyalgia syndrome. J Psychosom Res. 70(2):125-134. "The data suggest impaired autonomic cardiovascular regulation in FMS in terms of reduced sympathetic and parasympathetic influences, as well as blunted sympathetic reactivity to acute stress. The association between baroreflex function and pain experience reflects the pain inhibition mediated by the baroreceptor system. Given the reduced baroreflex sensitivity in FMS, one may assume deficient ascending pain inhibition arising from the cardiovascular system, which may contribute to the exaggerated pain sensitivity of FMS."

Reyes Del Paso GA, Montoro CI, Duschek S. 2015. Reaction time, cerebral blood flow, and heart rate responses in fibromyalgia: Evidence of alterations in attentional control. J Clin Exp Neuropsychol. 31:1-15. "Patients' clinical pain severity was positively associated with RT (reaction time) and CBF (cerebral blood flow) responses; trait anxiety and insomnia were secondary negative predictors of CBF responses. The study provided evidence of a deficit in the alertness component of attention in FMS at behavioral, CBF, and autonomic levels. These results may be interpreted in terms of the neural efficiency hypothesis of intelligence (i.e., less efficient brain activation during cognition in FMS) and the interfering effect of clinical factors on cognition. Clinical factors such as pain, anxiety, and sleep disturbances can affect cognition in FMS by interfering with CBF adjustment to cognitive demands."

Reyes Del Paso GA, Pulgar A, Duschek S et al. 2011. Cognitive impairment in fibromyalgia syndrome: The impact of cardiovascular regulation, pain, emotional disorders and medication. Eur J Pain. [Dec 19 Epub ahead of print]. "Thirty-five patients with FMS and 29 matched healthy controls completed a neuropsychological test measuring attention and arithmetic processing. As possible factors underlying the expected cognitive impairment, clinical pain intensity, co-morbid depression and anxiety disorders, sleep complaints, medication use, as well as blood pressure parameters were investigated. The patients' test performance was substantially reduced, particularly in terms of lower speed of cognitive processing and restricted improvement of performance in the course of the task. While the extent of depression, anxiety, fatigue and sleep complaints was unrelated to test performance, better performance was observed in patients showing lower pain ratings and those using opiate medication. The data corroborate the presence of substantial cognitive impairment in FMS. While the experience of chronic pain is crucial in mediating the deficits, co-morbid depression, anxiety, fatigue and sleep complaints play only a subordinate role. In the control group, but not in the patients, blood pressure was inversely associated with mental performance. This finding is in line with the well known cognitive impairment in hypertension. The lack of this association in FMS confirms previous research showing aberrances in the interaction between blood pressure and central nervous function in the affected patients."

Reyes-Manzano CF, Lerma C2, Echeverría JC et al. 2018. Multifractal analysis reveals decreased non-linearity and stronger anticorrelations in heart period fluctuations of fibromyalgia patients. Front Physiol. 9:1118. "When compared to healthy controls, fibromyalgia patients display decreased nonlinearity and stronger anticorrelations in heart period fluctuations. These findings reinforce the hypothesis of the potential role of the dysfunctional autonomic nervous system in the pathogenesis of fibromyalgia." Free Article

Reynolds MD. 1981.  Myofascial trigger point syndromes in the practice of rheumatology.  Arch Phys Med Rehabil. 62(3):111-114.  “Pain referred from a muscle can mimic both pain from a joint and radicular pain associated with disease of spinal joints, leading to mistakes in diagnosis and in treatment.  When articular disease is present, it predisposes to myofascial trigger point (TP) syndromes.  With arthritis, TPs in muscles may result from decreased mobility with prolonged shortening of muscles, from abnormal mechanical stress on muscles and from stimuli arising in diseased joints.  During examination for signs of myofascial disorders, the numbers of tender points and of local twitch responses in women with rheumatoid arthritis were twice those found in women free of any rheumatic illness.  It is important to consider this high frequency of myofascial syndromes in persons with arthritis when treating pain or weakness which could be due to the muscles rather than the joints.  Conversely, it has been proposed, on theoretical and clinical grounds, that muscular TPs can cause joint disease.  This hypothesis has important implications for the treatment of arthritis.”  [Studies are linking TrPs with arthritic conditions, and have been doing so for some time.  They are going unnoticed.  ALL arthritis patients need assessment of co-existing TrPs to relieve them of unnecessary symptom burden. DJS]

Reynolds, M. D. 1984. Myofascial trigger points in persistent posttraumatic shoulder pain. South Med J 77(10):1277-1280.

Reynolds WS, Brown ET, Danford J et al. 2016. Temporal summation to thermal stimuli is elevated in women with overactive bladder syndrome. Neurourol Urodyn. [Jul 19 Epub ahead of print.] "In this preliminary study, we demonstrated that women with OAB refractory to primary and secondary therapies exhibited greater thermal cutaneous temporal summation than women without OAB symptoms. This suggests that central sensitization, indexed by temporal summation, may be an underlying factor contributing to OAB in some women." [Temporal summation to Second Pain is a critical part of FM development. DJS]

Rezaeian T, Mosallanezhad Z, Nourbakhsh MR et al. 2020. Effects of dry needling technique into trigger points of the sternocleidomastoid muscle in migraine headache: A randomized controlled trial. Am J Phys Med Rehabil. Jun 15. [Epub ahead of print] Three sessions of dry needling in the sternocleidomastoid muscle TrPs resulted in immediate reduction of headache.

Rha DW, Shin JC, Kim YK et al. 2011. Detecting local twitch responses of myofascial trigger points in the lower back muscles using ultrasonography. Arch Phys Med Rehabil. [Aug 11 Epub ahead of print]. "These findings suggest that ultrasonography was useful for detecting LTRs (local twitch responses) of MTrPs, especially for LTRs in the deep muscles. Ultrasound guidance may improve the therapeutic efficacy of trigger point injection for treating MTrPs in the deep muscles."

Rhee SH, Park SH, Ha SH et al. Treatment of severe pain in a patient with complex regional pain syndrome undergoing dental treatment under general anesthesia: A case report. J Dent Anesth Pain Med. 2019 Oct;19(5):295-300. "Complex regional pain syndrome (CRPS) is rare, characterized by pain from diverse causes, and presents as extreme pain even with minor irritation. General anesthesia may be required for dental treatment because the pain may not be controlled with local anesthesia. However, treatment under general anesthesia is also challenging. A 38-year-old woman with CRPS arrived for outpatient dental treatment under general anesthesia. At the fourth general anesthesia induction, she experienced severe pain resulting from her right toe touching the dental chair. Anesthesia was induced to calm her and continue the treatment. After 55 minutes of general anesthesia, the patient still complained of extreme toe pain. Subsequently, two administrations for intravenous sedation were performed, and discharge was possible in the recovery room approximately 5 h after the pain onset. The pain was not located at the dental treatment site. Although the major factor causing pain relief was unknown, ketamine may have played a role." [CRPS may not be as rare as indicated here, but this is an example of how difficult it can be to manage when advanced. DJS]

Rhodin A, Gronbladh L, Nilsson LH et al. 2005.  Methadone treatment of chronic non-malignant pain and opioid dependence – A long-term follow-up.  Eur J Pain [Epub ahead of print June 20]  “A structured methadone program can be used for treating chronic pain patients with opioid dependence improving pain relief and quality of life.  However, side effects and serious adverse events may limit the beneficial effects of the method.”

Rhudy JL, Lannon EW, Kuhn BL et al. 2019. Assessing peripheral fibers, pain sensitivity, central sensitization, and descending inhibition in Native Americans: main findings from the Oklahoma Study of Native American Pain Risk (OK-SNAP). Pain. [Oct 7 Epub ahead of print] "Native Americans (NAs) have a higher prevalence of chronic pain than other U.S. racial/ethnic groups, but there have been few attempts to understand the mechanisms of this pain disparity. This study used a comprehensive battery of laboratory tasks to assess peripheral fiber function (cool/warm detection thresholds), pain sensitivity (eg, thresholds/tolerances), central sensitization (eg, temporal summation), and pain inhibition (conditioned pain modulation) in healthy, pain-free adults (NA), and non-Hispanic Whites (NHW)…. These findings suggest that there are no group differences between healthy NAs and NHWs on peripheral fiber function, central sensitization, or central pain inhibition, but NAs may have greater sensitivity to cold pain. Future studies are needed to examine potential within-group factors that might contribute to NA pain risk." [Travell and Simons noted that Native Americans may have a greater incidence of short upper arms. I found common perpetuating TrP factors in some tribes such as insulin resistance, short upper arms, short lower legs, long torso, etc., going from NA vendor to vendor at pow-wows and finding multiple cases of FM and CMPD in every tent/booth. Different tribes can have different relatively common body shapes and perpetuating factors, and one cannot logically lump all Native Americans into one group. DJS]

Ribeiro LS, Proietti FA. 2004.  Interrelations between fibromyalgia, thyroid autoantibodies, and depression.  J Rheumatol. 31(10):2036-2040.  This study “...suggests an association between FMS and thyroid immunity.”

Ribel-Madsen S, Gronemann ST, Bartels EM et al. 2005.  Collagen structure in skin from fibromyalgia patients.  Int J Tissue React. 27(3):75-82. “There are some differences between the amino acid composition of skin proteins in fibromyalgia patients compared with controls.  The amount of collagen may be lower in skin from fibromyalgia patients, and collagen packing in the endoneurium may be less dense.”  [This research may hold a clue to why the skin of FMS patients reacts so differently than the skin of healthy people. DJS]

Ricci V, Ricci C, Gervasoni F, et al. From histoanatomy to sonography in myofascial pain syndrome: A EURO-MUSCULUS/USPRM approach. Am J Phys Med Rehabil. 2023 Jan 1;102(1):92-97. "Considering the emerging role of ultrasound examination as the natural extension of physical assessment for musculoskeletal disorders, we briefly revise the histological/anatomical features of trigger points and propose a standardized, multistep sonographic approach to myofascial pain. We also imply that the integrated clinical-ultrasound evaluation could be considered as a potential tool to discriminate different phases/subsets of this challenging pathology."

Rich BA. 1997.  A legacy of silence: bioethics and the culture of pain.  J Med Humanit. 18(4):233-259. “This article takes bioethicists to task for failing to recognize the undertreatment of pain as a major ethical, and not merely a clinical, failing of the medical profession.”  Yet “for over 20 years the medical literature has carefully documented the undertreatment of all types of pain by physicians.” [At last, it is not just the patients who are asking why. DJS]

Rich BA. 1997.  A legacy of silence: bioethics and the culture of pain.  J Med Humanit. 18(4):233-259.  “For over 20 years the medical literature has carefully documented the undertreatment of all types of pain by physicians.  During this same period, as the field of bioethics came of age, the phenomenon of undertreated pain received almost no attention from the bioethics literature.  This article takes bioethicists to task for failing to recognize the undertreatment of pain as a major ethical, and not merely a clinical, failing of the medical profession.  The factors contributing to undertreated pain in the clinical setting are considered, as well as the hazards posed by recent failures to address ethically questionable clinical practices.”

Richards JR, Richards IN, Ozery G et al. 2010. Droperidol Analgesia for Opioid-Tolerant Patients. J Emerg Med. [Sep 10 Epub ahead of print]. "Patients with acute and chronic pain syndromes such as migraine headache, fibromyalgia, and sickle cell disease represent a significant portion of emergency department (ED) visits. Certain patients may have tolerance to opioid analgesics and often require large doses and prolonged time in the ED to achieve satisfactory pain mitigation. Droperidol is a unique drug that has been successfully used not only as an analgesic adjuvant for the past 30 years, but also for treatment of nausea/vomiting, psychosis, agitation, sedation, and vertigo....Droperidol has myriad pharmacologic properties that may explain its efficacy as an analgesic, including: histamine antagonist, muscarinic and nicotinic cholinergic antagonist, anticholinesterase activity, sodium channel blockade similar to lidocaine, and ...opiate receptor potentiation.....Droperidol is an important adjuvant for patients who are tolerant to opioid analgesics."

Richardson K, Gonzalez Y, Crow H et al. 2012. The effect of oral motor exercises on patients with myofascial pain of masticatory system. Case series report. NY State Dent J. 78(1):32-37. "The following case series report explores the impact of oral motor exercises on the management of myofascial pain when used in conjunction with other treatment modalities. Oral motor exercises are used by speech-language pathologists to improve the strength, range of movement and coordination of the oral musculature during non-speech movements. The findings of this case series report suggest an opportunity exists for collaboration between speech-language pathologists and the 'traditional' TMD team." [It will be a new world when the speech-language pathologists discover TrPs. DJS]

Ridgway, K. 1999. Acupuncture as a treatment modality for back problems. Vet Clin North Am Equine Pract 15(1):211-21.

Riedel, W., H. Layka and G. Neeck. 1998. Secretory pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH, and LH in patients with fibromyalgia syndrome following systemic injection of the relevant hypothalamic-releasing hormones. Z Rheumatol 57 Suppl 2:81-7.

Rigaud J, Delavierre D, Sibert L et al. 2010. [General principles of the diagnostic approach to chronic postoperative pelvic and perineal pain.] Prog Urol 20(12:1139-1144.[French] "The aetieological and diagnostic assessment of chronic postoperative pelvic and perineal pain requires a detailed clinical analysis based on examination of the scars and analysis of the clinical signs of muscle and nerve lesions..... A test block of a nerve or trigger point is the main test performed to determine the level of the lesion responsible for pain. " [Trigger points again as the pain generator. When will the medical world get it? DJS]

Rigberg DA, Gelabert H. 2009.  The management of thoracic outlet syndrome in teenaged patients.  Ann Vasc Surg. 23(3):335-340.  A significant number of teenaged patients with thoracic outlet syndrome can be helped by TrP injection and other TrP therapy.  [Much surgery can be prevented if TRP therapy and control of perpetuating factors is done promptly and thoroughly. DJS]

Riley GP, Harrall RL, Constant CR et al. 1996.  Prevalence and possible pathological significance of calcium phosphate salt accumulation in tendon matrix degeneration.  Ann Rheum Dis. 55(2):109-115.

Riley JL 3rd, Cruz-Almeida Y, King CD et al. 2013. Age and race effects on pain sensitivity and modulation among middle-aged and older adults. J Pain. [Nov 13 Epub ahead of print.] "This study tested the effects of aging and race on responses to noxious stimuli using a wide range of stimulus modalities. The participants were 53 non-Hispanic Blacks and 138 non-Hispanic White adults, ages 45 to 76. The participants completed a single 3-hour sensory testing session where responses to thermal, mechanical, and cold stimuli were assessed. The results suggest that there are selected age differences, with the older group less sensitive to warm and painful heat stimuli than middle-aged participants, particularly at the knee. This site effect supports the hypothesis that the greatest decrement in pain sensitivity associated with aging occurs in the lower extremities. In addition, there were several instances where age and race effects were compounded, resulting in greater race differences in pain sensitivity among the older participants. Overall, the data suggest that previously reported race differences in pain sensitivity emerged in our older samples, and this study contributes new findings in that these differences may increase with age in non-Hispanic Blacks for temporal summation and both heat and cold immersion tolerance. We have added to the aging and pain literature by reporting several small to moderate differences in responses to heat stimuli between middle and older age adults."

Riley JL 3rd, Cruz-Almeida Y, Staud R et al. 2018. The effects of manipulating the inter-stimulus-interval on heat-evoked temporal summation of second pan across the age span. Pain. [Aug 28 Epub ahead of print] Temporal summation of second pain (TSSP) is a measure of central sensitization, among other things. When an initial pain occurs, pain level rises, it peaks, and then returns to its previous level. After sufficient negative stimulation to the central nervous system (such as pain or irritation) another bout of equivalent pain ("second pain") can cause the pain level to rise even higher, stay at peak or higher levels longer, and perhaps not return to previous levels at all. The central nervous system (brain and spinal cord, is sensitized. This study found that in middle aged and older aged subjects, compared to younger subjects, there was a lessening of time for sensitization to begin, the peaks remained high longer, and took longer to return to a lower level. This "would suggest slower decay of excitability in spinal neurons and infer increased risk for central sensitization with advancing age." This finding is significant when dealing with fibromyalgia patients of older age, and increases the importance of adequate pain control and prevention of further central sensitization.

Rios R, Zautra AJ. 2011. Socioeconomic disparities in pain: the role of economic hardship and daily financial worry. Health Psychol. 30(1):58-66. "Economic hardship was associated not only with greater exposure to daily financial worries but also with greater vulnerability to pain on days when daily financial worries were experienced."

Rivera, J., A. de Diego, M. Trinchet and A. Garcia Monforte. 1997. Fibromyalgia-associated hepatitis C virus infection. Br J Rheumatol 36(9):981-985.

Rivera J, Vallejo MA, Esteve-Vives J. 2012. Drug prescription strategies in the treatment of patients with fibromyalgia. Reumatol Clin. [May 17 Epub ahead of print]. [Article in English, Spanish]. "The introduction of anticonvulsants or antidepressants, in an isolated or combined form, produces a significant clinical improvement in FM patients. The most effective drug strategy is the introduction of both drugs at the same time. The least effective strategy is not to change the number of drug prescriptions."

Rivers WE, Garrigues D, Graciosa J et al. 2015. Signs and symptoms of myofascial pain: An international survey of pain management providers and proposed preliminary set of diagnostic criteria. Pain Med. [Jun 5 Epub ahead of print.] "Myofascial Pain Syndrome (MPS) is highly prevalent in pain medicine, yet there is no 'gold standard' or set of validated diagnostic criteria for clinical or research use. A survey collected clinician perspectives on MPS to foster the development of a formal case definition for empirical validation….Two hundred fourteen responses were received from 4,143 surveys mailed. The most essential components of MPS were tender spots that recreate symptoms when palpated. MPS was also associated with muscle stiffness, decreased range of motion of the affected joints, worsening symptoms with stress, palpable taut band or tender nodule, and referred pain with palpation of the tender spot. Diagnostic studies are reported to be useful for ruling out other pathology, but not to confirm the presence of the condition….These results were used to propose a set of preliminary diagnostic criteria; expert consensus for case definition and subsequent empirical validation are required for standardization in research and clinical management of MPS."

Rivner MH. 2001.  The neurophysiology of myofascial pain syndrome.  Curr Pain Headache Rep. 5(5):432-440.

Rizzi M, Atzeni F, Airoldi A et al. 2016. Impaired lung transfer factor in fibromyalgia syndrome. Clin Exp Rheumatol. 34(2 Suppl 96):114-119. "The aim of this study was to evaluate whether pulmonary diffusing capacity is impaired in patients with fibromyalgia (FM) as it is in those with other diseases characterized by autonomic nerve system (ANS) dysfunction such as type 1 diabetes…. FM impairs DLCO (diffusing lung factor) mainly as a result of a reduction in Vc (vital capacity), and that this defect is inversely proportional to the severity of the dysfunction suggesting a relationship between impaired DLCO and autonomic nerve dysfunction. [Some of the vital capacity differences could be the result of respiratory muscle TrPs. DJS]

Rizzi M, Radovanovic D, Santus P et al. 2017. Influence of autonomic nervous system dysfunction in the genesis of sleep disorders in fibromyalgia patients. Clin Exp Rheumatol. 35 Suppl 105(3):74-80. "Fifty female FM patients and 45 healthy subjects matched for age, gender and body mass index underwent a clinical, polysomnographic and autonomic profile evaluation at rest and during a tilt test in order to determine muscle sympathetic nerve activity (MSNA), plasma catecholamine levels, and the spectral indices of cardiac sympathetic (LFRR) and vagal (HFRR) modulation computed by means of the spectrum analysis of RR during sleep…..The FM patients had a higher heart rate (HR), more MSNA and a higher LF/HF ratio, and lower HFRR values at rest…, and showed no increase in MSNA, a smaller decrease in HFRR, and an excessive rate of syncope (46%) during the tilt test. Their sleep was less efficient…, and they had a higher proportion of stage 1 non-REM sleep …, experienced many arousals and periodic limb movements (PLMs) per hour of sleep… and a high proportion of periodic breathing…. Their cyclic alternating pattern (CAP) rate was significantly increased… During sleep, they had a higher HR and LF/HF ratio, and a lower HFRR….. The number of tender points, CAP rate, PB% and PLMI correlated positively with HR and the LF/HF ratio, and negatively with HFRR during sleep…. Our findings seem to show that sleep causes the same effects as a stressful test in FM patients. A vicious circle is created during sleep: pain increases sympathetic cardiovascular activation and reduces sleep efficiency, thus causing lighter sleep, a higher CAP rate, more arousals, a higher PLMI, and increasing the occurrence of PB, which gives rise to abnormal cardiovascular neural control and exaggerated pain sensitivity."

Roach S, Sorenson E, Headley B et al. 2012. The prevalence of myofascial trigger points in the hip in patellofemoral pain patients. Arch Phys Med Rehabil Nov 2 [Epub ahead of print] Patients with pain in the front of the knee have a much greater prevalence of trigger points bilaterally in the gluteus medius and quadratus lumborum muscles. They also had less hip abduction strength which TrP release therapy was not sufficient to increase.

Robbins MS, Kuruvilla D, Blumenfeld A et al. 2014. Trigger Point Injections for Headache Disorders: Expert Consensus Methodology and Narrative Review. Headache. [Aug 28 Epub ahead of print.] "Indications for TPIs (trigger point injections) may include many types of episodic and chronic primary and secondary headache disorders, with the presence of active trigger points (TPs) on physical examination. Contraindications may include infection, a local open skull defect, or an anesthetic allergy, and precautions are necessary in the setting of anticoagulant use, pregnancy, and obesity with unclear anatomical landmarks. The most common muscles selected for TPIs include the trapezius, sternocleidomastoid, and temporalis, with bupivacaine and lidocaine the agents used most frequently. Adverse effects are typically mild with careful patient and procedural selection, though pneumothorax and other serious adverse events have been infrequently reported….When performed in the appropriate setting and with the proper expertise, TPIs seem to have a role in the adjunctive treatment of the most common headache disorders. We hope our effort to characterize the methodology of TPIs by expert opinion in the context of published data motivates the performance of evidence-based and standardized treatment protocols."

Robbins SM, Cossette-Levasseur M, Kikuchi K et al. Neuromuscular activation differences during gait in patients with Ehlers-Danlos syndrome and healthy adults. Arthritis Care Res (Hoboken). 2019 Sep 9. [Epub ahead of print] "Ehlers-Danlos syndrome (EDS) is a group of genetic disorders affecting connective tissue and symptoms include joint and ligament laxity. The objectives were to compare muscle activation, joint angles, and spatiotemporal parameters during gait, and isometric strength between participants with EDS (hypermobility and classical subtypes) and healthy adults…. Alterations in muscle activation and spatiotemporal parameters during gait in patients with EDS may be a result impaired proprioception and balance, and muscle weakness. Interventions should target these deficits."

Roberts MB, Drummond PD. 2016. Sleep problems are associated with chronic pain over and above mutual associations with depression and catastrophizing. Clin J Pain. 32(9):792-799. "Given that sleep has an important and unique contribution to pain and physical function, it is important that sleep disturbances are addressed both in the assessment and treatment of chronic pain".

Robertson JA, Purple RJ, Cole P et al. 2016. Sleep disturbance in patients taking opioid medication for chronic back pain. Anaesthesia. 71(11):1296-1307. "Patients on high doses of opioids (greater than 100 mg morphine-equivalent/day) demonstrated distinctly abnormal brain activity during sleep suggesting that polysomnography is necessary to detect sleep disturbance in this population in the absence of irregular rest-activity behaviour. Night-time sleep disturbance is common in individuals suffering from chronic pain and may be further exacerbated by opioid treatment." Free Article [More studies are needed to distinguish if the patients on high-dose opioid treatment had sleep disturbances due to the opioid therapy or to the greater pain levels and other symptomology that required the opioid therapy. DJS]

Robin F, Cébron T, Letellier M et al. 2018. The effects of emotional content on source monitoring in fibromyalgia patients. J Gen Psychol. 20:1-23. "Source confusion refers to a person's failure to distinguish whether an event has been actually seen or simply imagined. Nevertheless, prior research has demonstrated a reduction of source confusion for negative arousing information. According to the emotional-congruence effect, this emotional benefit is likely observed in patients suffering from chronic pain... In a source-monitoring task, participants had to decide whether positive, negative, and neutral words were imagined or seen with a picture. The results showed recognition deficits and more source confusion for FMS patients compared to controls. Contrary to the hypothesis of negativity bias in fibromyalgia, patients exhibited enhanced recognition for both positive and negative words. Moreover, they showed better source memory for the imagined items than for those seen with a picture. Overall, these results indicate that FMS affects episodic memory." [France]

Robinson de Senna B, Marques LS, Franca JP et al. 2009.  Condyle-disk-fossa position and relationship to clinical signs and symptoms of temporomandibular disorders in women.  Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 108(3):e117-124.

Robinson ME, Craggs JG, Price DD et al. 2010. Gray Matter Volumes of Pain-Related Brain Areas are Decreased in Fibromyalgia Syndrome. J Pain. [Dec 9 Epub ahead of print]. "Fibromyalgia (FM) is a chronic, widespread musculoskeletal pain disorder that is very prevalent in the general population (approximately 5%). Accumulating evidence suggests that FM is associated with central pain processing abnormalities, i.e., central sensitization. Several previous studies of chronic pain patients, including FM, have shown gray matter atrophy of brain areas associated with sensory and affective pain processing. These findings, however, have not been confirmed in all FM studies. In this study, we investigated gray matter volumes of brain areas associated with pain-related areas of FM patients identified by functional brain imaging…. Using a more stringent analysis than other VBM (voxel-based morphometric) studies, we provide evidence for decreased gray matter volumes in a number of pain-related brain areas in FM. Although the mechanisms for these gray matter changes are presently unclear, they may contribute to some of the core features of this chronic disorder including affective disturbances and chronic widespread pain….Increasing evidence supports the association of chronic pain with accelerated gray matter atrophy in pain disorders like low back pain, IBS, and FM syndrome. However, cause-effect relationships between chronic pain and decreased gray matter volumes have not been established yet and will require future prospective studies."

Robinson RL, Kroenke K, Williams DA et al. 2013. Longitudinal observation of treatment patterns and outcomes for patients with fibromyalgia: 12-month findings from the REFLECTIONS study. Pain Med. [June 11 Epub ahead of print]. This was a study using data from 1700 patients based on subjective inventories by patients on pregabalin (12%) duloxetine (15.5%), minilcipran (7.9%) or tricyclic antidepressants (3.9%). The focus was on "unique drugs for fibromyalgia" with over 75% of the patients taking over two or more medications, but not necessarily those medications. Duloxene and minilcipran patients had fewer outpatient visits than the others, and patients reported satisfaction with their treatment and "their fibromyalgia medication". [Bold lettering is theirs.] In the conclusions, ALL of the fibromyalgia patients had "modest improvements, high resources, and medication use, and were satisfied with the care they received." Authors admitted that it was difficult to tell the difference among the groups of patients due to the "high rates of drub discontinuation and concomitant medication over the 12 month period" of the study. The study was financed by Eli Lilly and Company. [This study is included in annotated references because it is easy to see how it could be misconstrued and perhaps misused. When quoting studies, often the sponsors of the studies and their relation to the medications are not given. DJS]

Robinson RLS, Jones ML. 2006.  In search of pharmacoeconomic evaluation for fibromyalgia treatments: a review.  Expert Opin Pharmacother. 7(8):1027-1039.  This article mentions the significant disability, complexity and economic costs of FMS, and stresses the lack of cost/benefit medical studies on remedies for FMS and that patients may try “...multiple pharmacological and non-pharmacological therapies with questionable efficacy.”  One must take into consideration any biases, intentional or unintentional, built in to research articles, but readers may not always be aware of the source of the research.  This paper was financed by a pharmaceutical company and written by its scientists. 

Roch M, Morin M, Gaudreault N. 2020. The MyotonPRO: A reliable tool for quantifying the viscoelastic properties of a trigger point on the infraspinatus in non-traumatic chronic shoulder pain. J Bodyw Mov Ther. 2020 Oct;24(4):379-385. "Clinicians rely on palpation for locating and diagnosing trigger points in muscles. Measuring a trigger point with clinical palpation remains a challenge. There are currently no validated tools available in clinical practice to objectively measure a trigger point…. The presence of a trigger point within the infraspinatus muscle was identified on thirty-five individuals with non-traumatic chronic shoulder pain via palpation according to Travell and Simons criteria. Trigger and non-trigger points were marked within the same muscle and the viscoelastic properties of both points were independently measured twice with the MyotonPRO by two evaluators on two days…. The MyotonPRO can differentiate the viscoelastic properties of a trigger point from a non-trigger point. Our findings support the reliability of this myotonometer. This affordable and portable tool can be used to objectively measure viscoelastic properties of trigger points in the infraspinatus."

Rocha CB, Sanchez TG. 2012. [Efficacy of myofascial trigger point deactivation for tinnitus control] [Portuguese] Braz J Otorhinolaryngol 78(6):21-26. "Besides medical and audiological investigation, patients with tinnitus should also be checked for: 1) presence of myofascial pain surrounding the ear; 2) laterality between both symptoms; 3) initial decrease of tinnitus during muscle palpation. Treating this specific subgroup of tinnitus patients with myofascial trigger point release may provide better results than others described so far. [There must also be an understanding that bilateral TrPs can be interacting with tinnitus, and that TrPs in the areas of the neck and surrounding tissues may also contribute to tinnitus. DJS]

Rocha CA, Sanchez TG. 2007.  Myofascial trigger points: another way of modulating tinnitus.  Prog Brain Res. 166:209-214.  “Tinnitus is a multifaceted symptom that may have many causes…”  “Tinnitus can often be modulated by different kinds of stimuli.”  “In 56% of patients with tinnitus and MTPs, the tinnitus could be modulated by applying digital compression of such points, mainly those of the masseter muscle.”  “Compression of MTPs was most effective in patients who have had chronic pain earlier in the examined areas.”  [As tinnitus can be severe enough to cause suicidal ideation, disrupting lives significantly, it is ironic that some patients can be helped so easily, yet are not.  DJS]

Rock JM, Rainey CE. 2014. Treatment of nonspecific thoracic spine pain with trigger point dry needling and intramuscular electrical stimulation: a case series. Int J Sports Phys Ther. 9(5):699-711. "Myofascial trigger points (MTrPs) are a common occurrence in many musculoskeletal issues and have been shown to be prevalent in both subjects with nonspecific low back pain and whiplash associated disorder. Trigger point dry needling (DN) has been shown to reduce pain and improve function in areas such as the cervical and lumbar spine, shoulder, hip, and knee, but has not been investigated in the thoracic spine. The purpose of this case series was to document the use of DN with intramuscular electrical stimulation (IES) in subjects with nonspecific thoracic spine pain… The subjects were both active duty military males aged 31 and 27 years who self-referred to physical therapy for thoracic spinal pain. Physical examination demonstrated thoracic motor control dysfunction, tissue hypertonicity, and tenderness to palpation of bilateral thoracic paraspinal musculature in both subjects. This indicated the presence of possible MrTPs. Objective findings in the first subject included painful thoracic flexion and bilateral rotation in each of these planes of movement. Pain reduction was observed when postural demands of the spine and trunk musculature were reduced through positional changes. Patient 1 demonstrated pain with posterior to anterior (P/A) pressure at T9 to T12. The second subject had bilaterally limited and painful thoracic rotation actively with normal passive rotation and demonstrated pain with P/A pressure at T4 to T7….Both subjects demonstrated motor control dysfunctions and pain with P/A pressure in the thoracic spine. With the use of DN and IES, immediate reduction was seen in subject perceived symptoms, and pain free ROM was improved. Extended treatment and follow up was not plausible due to the high pace tempo and demands of their operational training schedule. With research indicating the influence of MTrPs on a multitude of musculoskeletal issues and the prevalence of thoracic spine pain, further research is indicated for examining the effects of DN and IES for motor control and painful conditions occurring in the thoracic spine." Free PMC Article

Rodgers KR, Gui, Dinulos MB et al. 2017. Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases. Sci Rep. 7:39636. "We retrospectively analyzed electronic medical records of patients with Ehlers-Danlos Syndrome hypermobility type (HEDS), including demographic information, workup, rheumatological diagnoses in order to determine its association with rheumatological conditions. HEDS Patients were stratified according to level of workup received (no additional work (physical exam only) = NWU, limited workup = LWU, comprehensive workup = CWU)). HEDS patients were predominantly female (21:4, F:M). The percentage of patients with at least one rheumatological condition was significantly correlated with level of workup …. The HLA-B27 antigen was more prevalent… in the CWU HEDS patients (23.9%) than in the general population of the United States (6.1%). HEDS with CWU were associated with more rheumatological conditions (i.e. psoriasis, ankylosing spondylitis, rheumatoid arthritis, fibromyalgia) than those with NWU or LWU. In conclusion, HEDS is associated with complicated rheumatological conditions, which are uncovered by comprehensive workup. These conditions require different clinical management strategies than HEDS, and left untreated could contribute to the pain or even physical disability (i.e. joint erosions) in HEDS patients. While the mechanisms underlying these associations are unknown, it is important that all HEDS patients receive adequate workup to ensure a complete clinical understanding for the best care strategy possible." Free PMC Article

Rodham K, Rance N, Blake D. 2010. A qualitative exploration of carers' and 'patients' experiences of fibromyalgia: one illness, different perspectives. Musculoskeletal Care. [Mar 15 Epub ahead of print]. “This study aimed to explore the lived experiences of both those with FMS and their spousal carers…. . An overriding theme running throughout was loss of identity, which fed into a sense of isolation. Participants reported feeling isolated from: healthcare professionals, whom they felt they had to convince that they had something 'real', and from friends and family because the unpredictability of their symptoms meant that they were less able to plan ahead and often had to pull out of arranged outings. They also felt isolated from their identity because they no longer recognized the person that they once were, and struggled to recognize the person that they had become. As a consequence, the people with FMS and their carers were both engaged in a process of reassessing who they were, now that FMS had become such a large part of their lives. This sense of isolation was evidenced for the carers as well as the people with FMS….”

Rodreguez-Andreu J, Ibanez-Bosch R, Portero-Vasquez A et al. 2009.  Cognitive impairment in patients with fibromyalgia syndrome as assessed by the Mini-Mental State Examination.  BMC Musculoskeletal Disord. 10(1):162.  “Compared with the population reference value, patients with FMS showed high frequency of cognitive impairment.”

Rodrigo L, Blanco I, Bobes J et al. 2013. Clinical impact of a gluten-free diet on health-related quality of life in seven fibromyalgia syndrome patients with associated celiac disease. BMC Gastroenterol. 13(1):157. "Celiac disease (CD) is an autoimmune disorder, characterized by the presence of gastrointestinal and multisystem symptoms, which occasionally mimic those of Irritable Bowel Syndrome (IBS) and Fibromyalgia Syndrome (FMS). To assess the effectiveness of a Gluten-Free Diet (GFD) in seven adult female screening-detected CD subjects, categorized as severe IBS and FMS patients….Results of this pilot study show that the adherence to a GFD by CD-related IBS/FMS patients can simultaneously improve CD and IBS/FMS symptoms, and indicate the merit of further research on a larger cohort."

Rodrigo L, Blanco I, Bobes J et al. 2013. Remarkable prevalence of celiac disease in patients with irritable bowel syndrome plus fibromyalgia in comparison with those with isolated irritable bowel syndrome: a case-finding study. Arthritis Res Ther. 15(6):R201. "The findings of this screening indicate that a non-negligible percentage of IBS/FMS patients are CD patients, who can improve symptoms and possibly prevent long-term CD-related complications with a strict lifelong GFD."

Rodríguez A, Tembl J, Mesa-Gresa P et al. 2017. Altered cerebral blood flow velocity features in fibromyalgia patients in resting-state conditions. PLoS One. 12(7):e0180253. "The anterior and middle cerebral arteries of both hemispheres from 15 women with fibromyalgia and 15 healthy women were monitored using Transcranial Doppler (TCD) during a 5-minute eyes-closed resting period. Several signal processing methods based on time, information theory, frequency and time-frequency analyses were used in order to extract different features to characterize the CBFV signals in the different vessels. Main results indicated that, in comparison with control subjects, fibromyalgia patients showed a higher complexity of the envelope CBFV and a different distribution of the power spectral density. In addition, it has been observed that complexity and spectral features show correlations with clinical pain parameters and emotional factors…. These findings indicate that CBFV signals, specifically their complexity and spectral characteristics, contain information that may be relevant for the assessment of fibromyalgia patients in resting-state conditions." Free Article

Roehrs T, Diederichs C, Gillis M et al. 2015. Effects of reduced time in bed on daytime sleepiness and recovery sleep in fibromyalgia and rheumatoid arthritis. J Psychosom Res. [Mar 22 Epub ahead of print.] "Compared to RA and HC (healthy controls), people with FM responded to reduced bedtime with a comparable increase in sleepiness and greater recovery sleep efficiency, suggesting that homeostatic sleep mechanisms are functional in FM. People with FM uniquely showed REM rebound on recovery from reduced bedtime suggesting underlying REM pressure."

Roehrs T, Diederichs C, Gillis M et al. 2012. Nocturnal sleep, daytime sleepiness and fatigue in fibromyalgia patients compared to rheumatoid arthritis patients and healthy controls: A preliminary study. Sleep Med. [Nov 10 Epub ahead of print]. "Women with FM have similar nocturnal sleep disturbance as those with RA (rheumatoid arthritis), but FM patients report greater self-rated daytime sleepiness and fatigue than RA and HC, which did not correspond to the relatively low level of objectively determined daytime sleepiness of FM patients. These findings suggest a generalized hyperarousal state in FM."

Roehrs T, Hyde M, Blaisdell B et al. 2006.  Sleep loss and REM sleep loss are hyperalgesic.  Sleep. 29(2):145-151.  “...the loss of four hours of sleep and specific REM sleep loss are hyperalgesic the following day.  Pharmacologic treatments and clinical conditions that reduce sleep and REM sleep time may increase pain.”

Roehrs T, Withrow D, Koshorek G et al. 2020. Sleep and Pain in Subjects with Fibromyalgia and Comorbid Insomnia: Double-blind, Crossover, Study of Suvorexant 20 mg versus Placebo. J Clin Sleep Med. [Jan 14 Epub ahead of print] "Suvorexant (Belsomra) 20 mg in patients with fibromyalgia, improved sleep time and reduced next-day pain sensitivity on assessments of FWL to a radiant heat stimulus."

Roehrs TA. 2009. Does effective management of sleep disorders improve pain symptoms? Drugs. 69 Suppl 2:5-11. “Co-morbid insomnia is a much more frequent problem than primary insomnia. In co-morbid insomnia, management of the underlying disease can improve sleep difficulty. Conversely, treating the sleep disorder may also improve the co-morbid condition. For example, patients with painful chronic illnesses are more likely to experience sleep disturbance than patients with non-painful illnesses. Moreover, there is evidence that insomnia further exacerbates pain in these illnesses. This suggests that a reciprocal relationship exists between pain and sleep, and that intervention targeted primarily at insomnia may improve pain. Treatment options for sleep disorders in the context of pain that have been assessed include cognitive behavioral therapy for insomnia and various pharmacological therapies. In randomized clinical trials, cognitive behavioral therapy significantly improved insomnia secondary to chronic pain compared with control therapy, but pain was only improved in patients in whom it was associated with pain disorders other than fibromyalgia. Of the pharmacological agents studied (zopiclone, zolpidem and triazolam), only triazolam improved both sleep and pain to a greater extent than placebo. Overall, clinical data supporting a cause-effect relationship between insomnia and pain are preliminary and are limited to several small trials. Further investigation is required to clarify the extent of the link between insomnia and pain and whether successfully managing insomnia secondary to pain improves pain symptoms. Areas of particular interest include investigation of the effect of sleep agents on analgesia and the effect of analgesics on sleep.”

Rogal SS, Bielefeldt K, Wasan AD et al. 2014. Fibromyalgia Symptoms and Cirrhosis. Dig Dis Sci. [Nov 30 Epub ahead of print.] "A significantly high percentage of patients with nonalcoholic steatohepatitis (NASH) met the criteria for fibromyalgia and psychiatric symptoms. If abdominal pain was included in the model, etiology (the cause of cirrhosis) became non- significant, indicating that it may be central sensitization due to abdominal pain in patients with chronic liver disease that explains fibromyalgia symptoms rather than the etiology of liver disease or inflammation….Future work should focus on the underlying pathophysiology and management of widespread pain in patients with cirrhosis."

Rogalski MJ, Kellogg-Spadt S, Hoffmann AR et al. 2010. Int Unrogynecol j PPelvic Floor Dysfunct [Epub ahead of print] Retrospective chart review of vaginal diazepam suppository in high-tone pelvic floor dysfunction.  Diazepam suppositories can be a helpful accessory treatment for tight pelvic floor muscles.  [This supports use of topical diazepam or carisoprodol used inside the vagina and/or rectum as an adjunct treatment for pelvic floor muscles tightened by TrPs. DJS]

Rogers JL, Eudy AM, Pisetsky D et al. 2020. Utilizing clinical characteristics and patient-reported outcome measures to categorize lupus subtypes. Arthritis Care Res (Hoboken). [Jan 7 Epub ahead of print] "The Type 1 and Type 2 SLE categorization system was recently proposed in order to validate the patients' perspective of disease and to capture a more comprehensive spectrum of symptoms. The objective of this study was to characterize the clinical manifestations of SLE subtypes and to determine the correlation between the patient- and physician-reported measures used in the model…. Regardless of SLE disease activity, patients with FM (21%), reported higher SLAQ scores, patient global assessment scores, and self-reported lupus flare which resulted in discordance between patient- and physician- reported measures…." The usual methods of SLE assessment might require re-evaluation to include a subset of patients who have co-existing FM."

Rogozhin AA, Devlikamova FI. 2007.  Inactivation of trigger points could significantly reduce radicular pain.  J Musculoskel Pain 15 (Supp 13):35 item 59.  [Myopain 2007 Poster]  “It is difficult to distinguish between radicular and MPS because trigger points [TrPs] are widely present in patients with radiculopathy.”  “We can suppose that radicular pain in patients with acute radiculopathy partly could be caused by activation of TrPs.  Inactivation of TrPs in patients with radiculopathy never leads to complete pain relief but could be useful in patients with prolonged time course of disease.”  [The patient must be treated, rather than the radiography.  This means that soft tissue problems such as MTPs must be treated rather than the current focus on the skeletal system and discs alone.  DJS.]

Roitenberg N, Shoshana A. 2019. Physiotherapists' accounts of fibromyalgia: role-uncertainty and professional shortcomings. Disabil Rehabil. 30:1-8. "The study findings expose two overarching themes: (a) fibromyalgia as an ambiguous and uncertain diagnosis: physiotherapists devalue the diagnosis, referring to it as a syndrome rooted on psychological factors; (b) role ambiguity and creativity in physiotherapy treatment: by questioning their role, physiotherapists end up focusing on illness management and developing creative treatments. Conclusions: The study concludes that treating fibromyalgia patients challenges physiotherapists, mainly because of professional shortcomings. The findings highlight the necessity to train physiotherapists to respond to the needs of their patients with greater competence and less ambivalence…. Health providers need to acknowledge the difficulty physiotherapists are facing when providing treatment to fibromyalgia patients. Physiotherapists treating fibromyalgia should undergo special training to reduce their uncertainty and role ambiguity. Health providers should improve communication between physiotherapists and the General Practitioners referring fibromyalgia patients, to enable them to set shared evidence-based treatment goals."

Roldan CJ, Hu N. 2015. Myofascial pain syndromes in the Emergency Department: What are we missing? J Emerg Med. [Jul 4 Epub ahead of print.] "Myofascial pain syndrome (MPS), pain originating in the myofascial tissue, is a widely recognized pathology characterized by the presence of referred pain (often distant from its origin and specific to each muscle) that can resemble other pathologies and by the presence of a trigger point, a localized hyperirritable band able to reproduce the pain and its associated symptoms. Patients with acute or chronic MPS are commonly seen in the emergency department (ED), usually complaining of pain of undetermined origin. Traditionally, the emergency physician (EP) is not trained to diagnose and treat MPS, and many patients with MPS have received less than optimal management of this condition in the ED. Many types of treatments are known to be effective against MPS. Among these, trigger point injection (TPI) is considered a practical and rapid approach that can be carried out in the ED by EPs….MPS can mimic other clinical conditions commonly seen in the ED. MPS can be diagnosed on the basis of clinical findings; in many cases, no imaging or laboratory testing is needed. Therefore, MPS diagnosis and treatment can be successfully accomplished in the ED by EPs."

Roldan CJ, Huh BK. 2016. Iliocostalis thoracis-lumborum myofascial pain: Reviewing a subgroup of a prospective, randomized, blinded trial. A challenging diagnosis with clinical implications. Pain Physician. 19(6):363-372. "Pain of myofascial origin is a well-recognized pathology characterized by the presence of two components: referred pain; which is often distant from its source and specific to each muscle, and the trigger point, a localized hyperirritable band present in the affected muscle and able to reproduce the referred pain when stimulated. Myofascial pain (MP) commonly coexists in patients with acute or chronic pain of other etiologies. The uniqueness of the clinical presentation of some MPs and the lack of training of most specialties represent a clinical challenge. Thus, many patients with MPS receive less than optimal management of this condition….Pain at the anterior torso, originating at the posterior torso, can mimic common pathologies that correlate with the same anatomical area such as cardiac and intra-abdominal conditions. These clinical characteristics could be caused by MP of the iliocostalis thoracis-lumborum (ITL) muscle. (These muscles are part of the thoracocolumbar paraspinals, also called erector spinae.)…. A convenience sample of 43 patients who presented to the ED with pain at the anterior aspect of the torso (chest, abdomen, or pelvis) and clinical evidence of MP originated in the ITL muscle. Of a clinical trial of patients with MP, we describe a subgroup of patients with MP of the ITL which was clinically evident by the presence of a trigger point (TP) in its ability to reproduce the referred pain present at the anterior aspect of the torso. Patients received a TP injection. In this trial we intend to demonstrate that TP injections using particulate steroids mixed with a local are no more effective than saline alone to treat MP. The primary outcome was pain control (decrease in intensity of 50% or more below baseline numeric pain rating). A follow-up telephone interview was performed by third-party abstractors. RESULTS: Forty-three patients presented with pain of the anterior torso and ipsilateral back, both correlating with the level of the TP of the ITL muscle. The pain had been present from 2 days to 7 years. The most common locations of pain were the right-lower quadrant and the left side of the chest. In many of them a pattern of missed diagnosis was evident despite extensive workups and consultations. Only 17 patients were able to identify the precipitating event; the most common was coughing. Two weeks after TP injection, all patients still had satisfactory pain control. After treatment, no missed pathology or returns to the ED were reported….CONCLUSIONS: Anterior torso pain often resulted in extensive workups before ITL myofascial pain was diagnosed. TP injections were diagnostic and therapeutic of ITL myofascial pain." Free Article [If patients at other EDs or ERs were thus evaluated and treated, there might be less chronic pain. This procedure is what I recommended in my last book. DJS]

Roldan CJ, Osuagwu U, Cardenas-Turanzas M et al. 2019. A randomized blind controlled non-inferiority trial to compare the effectiveness of trigger point injections performed with normal saline (NS) and conventional active drug mix (CADM) in patients with myofascial pain syndromes. Am J Emerg Med. 24:158410. "Myofascial pain syndrome (MPS) originates in the muscle and fascia. MPS presents with referred pain specific for each muscle and a trigger point that reproduces the symptoms. Trigger-point-injection (TPI) is an effective approach to treating MPS. Some TPI agents, however, are associated with systemic and local side effects….In cases of MPS in the ED, pain can be controlled with TPI independent of the injectate. TPI with NS may be preferred over CADM because of its lower cost and more favorable side effect profile." [Results may differ in patients who have Chronic Myofascial Pain and Dysfunction, FM, and/or CRPS. If central sensitization is already involved, pain must be minimized to prevent further central sensitization. More research is encouraged. DJS]

Roldan-Jimenez C, Perez-Cruzado D, Neblet R, et al. Central Sensitization in Chronic Musculoskeletal Pain Disorders in Different Populations: A Cross-Sectional Study. Pain Med. 2020 Mar 31. [Epub ahead of print] Of 395 Spanish participants with chronic musculoskeletal pain disorders, there was a "high prevalence of clinically relevant" scores for central sensitization, especially in those with neck and low back pain.

Romanello S, Spiri D, Mancuzzi E et al. 2013 Association between childhood migraine and history of infantile colic. JAMA. 309(15):1607-1612. Infant with colic have a grater chance of developing migraines between 6 and 18 years old. The association between these types of pain is yet unknown to these researchers. [Janet Travell long ago documented that trigger points causing colic can be relieved by vapocoolant spray, and other researchers have documented the connection of trigger point cause or contribution to migraines. The great Czech doctor Karel Lewit MD has observed that colic is an early indication that trigger points will develop later, and that migraines (and menstrual pain) are adolescent signs that trigger points will be part of the diagnoses. Perhaps that is the connection for which these researchers search, and perhaps early detection and treatment of the TrPs would prevent chronic myofascial pain from developing. It certainly would be worth trying. DJS]

Romano GF, Tomassi S, Russell A et al. 2015. Fibromyalgia and chronic fatigue: the underlying biology and related theoretical issues. Adv Psychosom Med. 34:61-77. "There is an increasing interest in understanding the biological mechanism underpinning fibromyalgia (FM) and chronic fatigue syndrome (CFS). Despite the presence of mixed findings in this area, a few biological systems have been consistently involved, and the increasing number of studies in the field is encouraging. This chapter will focus on inflammatory and oxidative stress pathways and on the neuroendocrine system, which have been more commonly examined. Chronic inflammation, together with raised levels of oxidative stress and mitochondrial dysfunction, has been increasingly associated with the manifestation of symptoms such as pain, fatigue, impaired memory, and depression, which largely characterize at least some patients suffering from CFS and FM. Furthermore, the presence of blunted hypothalamic-pituitary-adrenal axis activity, with reduced cortisol secretion both at baseline and in response to stimulation tests, suggests a role for the hypothalamic-pituitary-adrenal axis and cortisol in the pathogenesis of these syndromes. However, to what extent these systems' abnormalities could be considered as primary or secondary factors causing FM and CFS has yet to be clarified."

Romero-Zurita A, Carbonell-Baeza A, Aparicio VA et al. 2012. Effectiveness of a tai-chi training and detraining on functional capacity, symptomatology and psychological outcomes in women with fibromyalgia. Evid Based Complement Alternat Med. 2012:614196 [May 9 Epub ahead of print]. "A 28-week Tai-Chi intervention showed improvements on pain, functional capacity, symptomatology and psychological outcomes in female FM patients."

Romeyke T, Noehammer E, Scheuer HC et al. 2017. Severe forms of fibromyalgia with acute exacerbation of pain: costs, comorbidities, and length of stay in inpatient care. Clinicoecon Outcomes Res. 9:317-325. "Severe forms of fibromyalgia are accompanied by many concomitant diseases and associated with both high clinical staff costs and high medical and nonmedical infrastructure costs. Indication-based cost calculations provide important information for health policy and hospital managers if they include all elements that incur costs in both a differentiated and standardized way." Free Article

Ronconi G, De Giorgio F, Ricci E et al. 2016. [Pneumothorax following dry needling treatment: legal and ethical aspects]. Ig Sanita Pubbl. 72(5):505-512. [Article in Italian] "In this paper we describe the case of a professional swimmer who developed pneumothorax after dry needling treatment and discuss the medicolegal and ethical aspects related to competencies and responsibilities of medical doctors and physiotherapists performing the procedure."

Ronel D, Gabbay O, Esterson A et al. 2018. Twenty thousand needles under the sea. Trigger point dry needling aboard an Israeli Navy submarine: A case report. Mil Med. [Apr 4 Epub ahead of print] "Trigger point dry needling is a method of alleviating such pain by the introduction of needles into trigger points in muscles. A growing body of evidence supports its use in myofascial pain and specifically lower back pain. Submarine Medicine is a unique field due to the special characteristics and the environment of the submarine. It poses challenges that are not always seen by primary care physicians. Here, we present a case of a 40-yr-old senior submarine officer who complained of pain in his lower back and pelvis before departing on a mission. The pain persisted in spite of treatment with nonsteroidal anti-inflammatory drugs and he was then treated by the submarine's physician with trigger point dry needling. The officer showed rapid improvement following this treatment, both regarding pain and the range of motion."

Roost M, Nilsson P. 2002.  [Sleep disorders — a public health problem.  Potential risk factor in the development of type 2 diabetes, hypertension, dyslipidemia and premature aging]  Lakartidningen 99(3):154-157. [Swedish]  “Sleep disorders may play a primary role in the pathophysiology of cardiovascular disease.  This has recently been documented in association with metabolic disturbances and impaired insulin action following experimental sleep deprivation.  Sleep disorders may finally prove to be part of the pathophysiological chain linking adverse psychosocial stress with the metabolic syndrome, and ultimately premature aging and early mortality.”

Rosado-Pérez J, Santiago-Osorio E, Ortiz R et al. 2012. Tai chi diminishes oxidative stress in Mexican older adults. J Nutr Health Aging. 16(7):642-646. "...the daily practice of Tai Chi is useful for reducing OxS (oxidative stress) in healthy older adults."

Rosenbaum TY. 2009.  Musculoskeletal pain and sexual function in women.  J Sex Med. [Sep 14 Epub ahead of print]  “Musculoskeletal pain (MP) that is not essentially genitally based often interferes with sex as well yet is not considered a distinct sexual dysfunction.  MP is generally addressed by physiatrists, orthopedists, and rheumatologists who are not traditionally trained in sexual medicine, and therefore, the sexual concerns of women with MP often go unaddressed.”  “Lack of mobility and MP can restrict intercourse and limit sexual activity, and gender differences are noted in response to pain.  Sexual and relationship counseling should be offered as a component of rehabilitative treatment.  Physical therapists are uniquely qualified to provide treatment to address functional activities of daily living, including sexual intercourse, and offer advice for modifications in positioning.”

Rosenbaum TY. 2009.  Musculoskeletal pain and sexual function in women.  J Sex Med. [Sep 14 Epub ahead of print].  “Lack of mobility and MP (musculoskeletal pain) can restrict intercourse and limit sexual activity, and gender differences are noted in response to pain.  Sexual and relationship counseling should be offered as a component of rehabilitative treatment.  Physical therapists are uniquely qualified to provide treatment to address functional activities of daily living, including sexual intercourse, and offer advice for modifications in positioning.”  [Future studies will be greatly enhanced if myofascial trigger point assessment and remediation would be included. DJS]

Rosenberg RP, Benca R, Doghramji P, et al. A 2023 update on managing insomnia in primary care: insights from an expert consensus group. Prim Care Companion CNS Disord. 2023;25(1):22nr03385. "Insomnia is highly prevalent but underdiagnosed and undertreated. It is increasingly recognized as a distinct disorder, not merely a symptom arising secondary to another medical or psychiatric illness. The subtypes of sleep disturbance-reports of difficulty falling or staying asleep, insufficient sleep duration, early waking-and the presence of next-day impairment and common comorbid conditions require a targeted, individualized approach to therapy…. Optimal outcomes for insomnia require a comprehensive approach that includes lifestyle and behavioral strategies to mitigate maladaptive thoughts and behaviors related to sleep and selection of pharmacotherapy based on individual patient complaints and characteristics."[Lack of restorative sleep is linked with chronic musculoskeletal pain. Insomnia in all its forms is a major perpetuating factor that deserves to be respected and treated. DJS]

Rosenfeld V, Rutledge D, Stern JM. 2014. Polysomnography with Quantitative EEG in Patients with and without Fibromyalgia. J Clin Neurophysiol. [Sep 16 Epub ahead of print.] "All undergoing all-night polysomnography for evaluation of a sleep disorder were evaluated for fibromyalgia. The polysomnograms were interpreted for routine sleep measures and qEEG was performed to measure the delta and alpha frequency power during non-REM sleep. Measures and qEEG were analyzed according to fibromyalgia diagnosis….Sleep disorders identified by routine polysomnography, including obstructive sleep apnea, are common in fibromyalgia, but periodic leg movement disorder and poor sleep efficiency are not. A qEEG low delta/alpha ratio during non-REM sleep can differentiate patients with fibromyalgia from others who are referred for polysomnography. Consideration of benzodiazepine and benzodiazepine agonist use is important when interpreting the delta/alpha ratio."

Rosengren SM, Colebatch JG. 2010. Vestibular evoked myogenic potentials are intact in cervical dystonia. Mov Disord. [Oct 19 Epub ahead of print]. "Vestibular dysfunction has been reported in patients with cervical dystonia (CD), but it is still unclear whether the abnormalities occur as part of the CD syndrome or whether they arise from the abnormal posture and movement of the head..... Both cervical and ocular VEMPs (vestibular-evoked myogenic potentials) were present in the majority of patients and controls..... Our results showed that VEMPs can be reliably recorded from both the neck and extraocular muscles in patients with CD, even after long disease or treatment durations, and provide evidence for intact short-latency vestibular reflexes in CD. " [FM, TrPs and vestibular dysfunction ar often interactive co-existing conditions. DJS]

Rosenhall, U., G. Johansson and G. Orndahl. 1996. Otoneurologic and audiologic findings in fibromyalgia. Scan J Rehabil Med 28(4):225-232.

Roskos SE, Keenum AJ, Newman LM et al. 2007.  Literacy demands and formatting characteristics of opioid contracts in chronic nonmalignant pain management.  J Pain [Mar 21 Epub ahead of print]   “Most OCs contained not only sophisticated medical language but multisyllable, nonmedical terms and vocabulary not used in typical everyday conversation.”  Opioid contracts must be understandable and clear, and this is not the case.

Ross JL, Queme LF, Cohen ER et al. 2016. Muscle IL1β drives ischemic myalgia via ASIC3-mediated sensory neuron sensitization. J Neurosci. 36(26):6857-6871. Although muscle pain is common, we don't know the exact mechanisms involved in creating pain from lessened blood flow. This study in mice found that lack of sufficient blood flow caused pain dependent on changes in acid-sensing ion channels. These channels in the cellular membranes are like tunnels with airlocks, allowing mineral salts such as potassium and calcium into and out of the cell. These acid-sensing ion channels were activated by interleukin 1 beta, which may be a new target for muscle pain relief and alternative therapies. "Here, we have described a novel pathway whereby increased inflammation within the muscle tissue during ischemia/reperfusion injury sensitizes group III and IV muscle afferents via upregulation of acid-sensing ion channel 3 (ASIC3), leading not only to alterations in mechanical and chemical responsiveness in individual afferents, but also to pain-related behavioral changes." (This) "…may be especially relevant to pain caused by issues of peripheral circulation, which is commonly observed in disorders such as complex regional pain syndrome, sickle cell anemia, or fibromyalgia."

Ross JL, Queme LF, Lamb JE et al. 2018. Sex differences in primary muscle afferent sensitization following ischemia and reperfusion injury. Biol Sex Differ. 9(1):2. "Females have more mechanically sensitive muscle afferents and show greater mechanical and thermal responsiveness than what is found in males.....Here, we illustrate a unique phenomenon wherein discrete, sex-dependent mechanisms of primary muscle afferent sensitization after ischemic injury to the periphery may underlie similar behavioral changes between the sexes.....Hence, this study illustrates the pressing need for further exploration of sex differences in afferent function throughout the lifespan for use in developing appropriately targeted pain therapies." Free Article

Ross V, Detterman C, Hallisey A. 2021. Myofascial pelvic pain: An overlooked and treatable cause of chronic pelvic pain. J Midwifery Womens Health. Mar 31. Online ahead of print. "Myofascial pelvic pain is involved in an estimated 22% to 94% of cases of chronic pelvic pain, which is one of the most common gynecologic conditions in the United States. Myofascial pelvic pain may exist independently or in conjunction with disorders such as vaginismus, dysmenorrhea, and endometriosis and is frequently a causative factor in sexual pain or dyspareunia."

Rossi DM, Morcelli MH, Marques NR et al. 2014. Antagonist coactivation of trunk stabilizer muscles during Pilates exercises. J Bodyw Mov Ther. 18:34-41. Pilates practitioners must be aware that some of their strategies could make some patients worse. One must be aware of compensatory muscle recruitment and other adjustments the body has made. [This is often due to trigger points.] "This suggests that the exercises of Skilled Modern Pilates only should be performed after appropriate learning and correct execution of all principles, mainly the Centering Principle."

Rossi M, DeCarolis G, Liberatoscioli G et al. 2016. A novel mini-invasive approach to the treatment of neuropathic pain: The PENS Study. Pain Physician. 19(1):E121-128. "Peripheral neuromodulation is often used as chronic neuropathic pain treatment. Percutaneous electrical nerve stimulation (PENS) is generally utilized with several probes at the same time and repeated treatments…..Seventy-six patients (47 women, 29 men), mean age 62…, affected by neuralgia (21 herpes zoster infection, 31 causalgia, 24 postoperative pain) were enrolled in the study (in 4 Italian pain centers)….After localization of trigger point and/or allodynic/ hyperalgesic area, PENS therapy was achieved with a single 21 gauge conductive probe tunneled percutaneously and a neurostimulator device….PENS therapy produced significant and long-lasting pain relief in chronic peripheral neuropathic pains of different etiology." Free Article

Roth, T. and S. Ancoli-Israel. 1999. Daytime consequences and correlates of insomnia in the United States: results of the 1991 National Sleep Foundation Survey. II. Sleep 22 Suppl 2:S354-8.

Roumen RMH, Vening W, Wouda R et al. 2017. Acute appendicitis, somatosensory disturbances ("Head Zones"), and the differential diagnosis of Anterior Cutaneous Nerve Entrapment Syndrome (ACNES). J Gastrointest Surg. [Apr 14 Epub ahead of print] "Anterior cutaneous nerve entrapment syndrome (ACNES) is a neuropathic abdominal wall pain syndrome typically characterized by locally altered skin sensations. On the other hand, visceral disease may also be associated with similar painful and altered skin sensations ("Head zones")…. A substantial portion of patients with acute appendicitis demonstrate right lower abdominal somatosensory disturbances that are similar as observed in acute ACNES. Both may be different sides of the same coin and are possibly expressions of segmental phenomena as described by Head. McBurney's point, a landmark area of maximum pain in acute appendicitis, is possibly a trigger point within a Head zone. Differentiating acute appendicitis from acute ACNES is extremely difficult, but imaging and observation may aid in the diagnostic process."

Roussel NA, Nijs J, Meeus M et al. 2013. Central Sensitization and Altered Central Pain Processing in Chronic Low Back Pain: Fact or Myth? Clin J Pain. 29(7):625-638. "Results of studies examining the responsiveness to various stimuli in patients with chronic LBP (low back pain) are conflicting. Some studies in patients with chronic LBP have demonstrated exaggerated pain responses after sensory stimulation of locations outside the painful region, while other studies report no differences between patients and healthy subjects. Studies examining the integrity of the endogenous pain inhibitory systems report unaltered activity of this descending inhibitory system. In contrast, studies analyzing brain structure and function in relation to (experimentally induced) pain provide preliminary evidence for altered central nociceptive processing in patients with chronic LBP. Finally, also psychosocial characteristics, such as inappropriate beliefs about pain, pain catastrophizing, and/or depression may contribute to the mechanisms of central sensitization. …It tempting to speculate that ongoing nociception is associated with cortical and subcortical reorganization and may play an important role in the process of the chronification of LBP. Future prospective research should explore to what extent these changes are reversible and if this reversibility is associated with improved functioning of patients."

Roussou E, Ciurtin C. 2012. Clinical overlap between fibromyalgia tender points and enthesitis sites in patients with spondyloarthritis who present with inflammatory back pain. Clin Exp Rheumatol. [Aug 30 Epub ahead of print]. "To assess the extent of coexistence of inflammatory back pain (IBP) with fibromyalgia (FM) features in patients with spondyloarthritis (SpA), and to assess the degree of overlap of FM tender points (TeP) and enthesitis sites (ES) in patients with SpA.....One third of patients with IBP fulfilled the criteria for FM. There is a significant degree of overlap between FM TeP and ES in patients with IBP.[Since many patients with FM have trigger points, and trigger points in the attachment areas cause enthesitis and enthesis, it would be helpful to know what percentage of these patients had TrPs and if the contracture from TrPs might cause the inflammation. DJS]

Rowe PC, Fontaine KR, Violand RL. 2013. Neuromuscular strain as a contributor to cognitive and other symptoms in chronic fatigue syndrome: hypothesis and conceptual model. Front Physiol. 4:115. "Individuals with chronic fatigue syndrome (CFS) have heightened sensitivity and increased symptoms following various physiologic challenges, such as orthostatic stress, physical exercise, and cognitive challenges. Similar heightened sensitivity to the same stressors in fibromyalgia (FM) has led investigators to propose that these findings reflect a state of central sensitivity. A large body of evidence supports the concept of central sensitivity in FM. A more modest literature provides partial support for this model in CFS, particularly with regard to pain. Nonetheless, fatigue and cognitive dysfunction have not been explained by the central sensitivity data thus far. Peripheral factors have attracted attention recently as contributors to central sensitivity. Work by Brieg, Sunderland, and others has emphasized the ability of the nervous system to undergo accommodative changes in length in response to the range of limb and trunk movements carried out during daily activity. If that ability to elongate is impaired-due to movement restrictions in tissues adjacent to nerves, or due to swelling or adhesions within the nerve itself-the result is an increase in mechanical tension within the nerve. This adverse neural tension, also termed neurodynamic dysfunction, is thought to contribute to pain and other symptoms through a variety of mechanisms. These include mechanical sensitization and altered nociceptive signaling, altered proprioception, adverse patterns of muscle recruitment and force of muscle contraction, reduced intra-neural blood flow, and release of inflammatory neuropeptides. Because it is not possible to differentiate completely between adverse neural tension and strain in muscles, fascia, and other soft tissues, we use the more general term "neuromuscular strain." In our clinical work, we have found that neuromuscular restrictions are common in CFS, and that many symptoms of CFS can be reproduced by selectively adding neuromuscular strain during the examination. In this paper we submit that neuromuscular strain is a previously unappreciated peripheral source of sensitizing input to the nervous system, and that it contributes to the pathogenesis of CFS symptoms, including cognitive dysfunction." [This is an interesting paper indicating that perhaps trigger points may be common in CFS, as they are in FM. DJS]

Roy-Byrne P, Smith WR, Goldberg J et al. 2004.  Post-traumatic stress disorder among patients with chronic pain and chronic fatigue.  Psychol Med 34(2):363-368.  "Optimal clinical care for patients with FMS should include an assessment of trauma in general, and PTSD in particular."

Royds J, Conroy MJ, Dunne MR et al. An investigation into the modulation of T cell phenotypes by amitriptyline and nortriptyline. Eur Neuropsychopharmacol. 2019 Dec 24. [Epub ahead of print.] This article desctibes the reason why amitriptyline and nortriptyline are useful for off-label conditions such as fibromyalgia. This work indicates these meds may involve the modulation of T-cells, and thus the immune system, by these medications often used in FM and other chronic pain conditions.

Rozenfeld E, Finestone AS, Moran U et al. 2017. Test-retest reliability of myofascial trigger point detection in hip and thigh areas. J Bodyw Mov Ther. 21(4):914-919. "Myofascial trigger points (MTrP's) are a primary source of pain in patients with musculoskeletal disorders. Nevertheless, they are frequently underdiagnosed. Reliable MTrP palpation is the necessary for their diagnosis and treatment. The few studies that have looked for intra-tester reliability of MTrPs detection in upper body, provide preliminary evidence that MTrP palpation is reliable.... Inter- and intra-tester reliability of active and latent MTrP evaluation was moderate to substantial. Palpation evaluation can be used for clinical diagnosis of MTrP's in the hip and thigh muscles....This study provides evidence that MTrP palpation is a moderately reliable diagnostic tool in the hip and thigh muscles and can be used in clinical practice and research."

Rra ML, Angst F, Beck T et al. 2012. Horticultural therapy for patients with chronic musculoskeletal pain: results of a pilot study. Altern Ther Health Med. 18(2):44-50. "Seventy-nine patients with chronic musculoskeletal pain (fibromyalgia or chronic, nonspecific back pain) participated in the study….The addition of horticultural therapy to a pain management program improved participants' physical and mental health and their coping ability with respect to chronic musculoskeletal pain."

Ruaro JA, Frez AR, Ruaro MB et al. 2014. Low-level laser therapy to treat fibromyalgia. Lasers Med Sci. [May 7 Epub ahead of print.] "LLLT provided relief from fibromyalgia symptoms in patients and should be further investigated as a therapeutic tool for management in fibromyalgia."

Rubic B. 2002.  The biofield hypothesis: its biophysical basis and role in medicine.  J Altern Complement Med 8(6):703-717.  “This paper provides a scientific foundation for the biofield: the complex extremely weak electromagnetic field of the organism hypothesized to involve electromagnetic bioinformation for regulating homeodynamics.”  This hypothesis may relate to the benefits of acupuncture, bioelectromagnetic and other complementary medicine methods.

Rudin NJ. 2003.  Evaluation of treatments for myofascial pain syndrome and fibromyalgia.  Curr Pain Headache Rep 7(6):433-442.  As the title suggests, this is a general evaluation of these conditions, although the author mentions early that there is a question of whether either of these conditions exist. Treatment options are discussed without mention of perpetuating factors, and they often are the chief clue to the tailoring of specific remedial work and treatment regimens.

Care is taken to note that treatments must be carefully tailored to the needs of the individual patient.  What is effective for some may not fill the needs of others, and some types of therapies require specific attention to protocol for success, and as the author states, no single therapeutic regimen will be successful on every patient.  There are many fine points to this article, but it is unfortunate that the difference between hypothyroid and thyroid-resistant states was not specified, and that the dismissal of guaifenesin was based on a single flawed study.

Ruggiero V, Mura M, Cacace E et al. 2017. Free amino acids in fibromyalgia syndrome: relationship with clinical picture. Scand J Clin Lab Invest. 12:1-8. "The objectives of our study were to evaluate free amino acid (FAA) concentrations in the serum of patients affected by fibromyalgia syndrome (FMS) and to determine the relationships between FAA levels and FMS clinical parameters. Thus, serum amino acid concentrations were quantified (HPLC analysis) in 23 females with fibromyalgia (according to the American College of Rheumatology classification criteria) and 20 healthy females. The results showed significantly higher serum concentrations of aspartate, cysteine, glutamate, glycine, isoleucine, leucine, methionine, ornithine, phenylalanine, sarcosine, serine, taurine, tyrosine and valine in FMS patients vs. healthy controls. Patients with higher Fibromyalgia Impact Questionnaire (FIQ) scores showed increased levels of alanine, glutamine, isoleucine, leucine, phenylalanine, proline and valine. In conclusion, our results indicate an imbalance in some FAAs in FMS patients. Increased Glu is particularly interesting, as it could explain the deficit in monoaminergic transmission involved in pain." [One must be careful in supplementing. Supplementation only helps if you have an insufficiency in the substance supplemented, and can metabolize the dosage form of supplement. DJS]

Ruhl A. 2005. Glial cells in the gut. Neurogastroenterol Motil. 17(6):777-790.  “The enteric nervous system is composed of both neurons and glia.  Recent evidence indicates that enteric glia—which vastly outnumber enteric neurons—are actively involved in the control of gastrointestinal functions: they contain neurotransmitter precursors, have the machinery for uptake and degradation of neuroligands, and express neurotransmitter-receptors which makes them well suited as intermediaries in enteric neurotransmission and information processing in the ENS.  Novel data further suggest that enteric glia have an important role in maintaining the integrity of the mucosal barrier of the gut.  Finally, enteric glia may also serve as a link between the nervous and immune systems of the gut as indicated by their potential to synthesize cytokines, present antigen and respond to inflammatory insults.”  “...it is predictable that enteric glia are involved in the etiopathogenesis of various pathological processes in the gut.”

Ruiz-Cabello P, Soriano-Maldonado A, Delgado-Fernandez M et al. 2016. Association of dietary habits with psychosocial outcomes in women with fibromyalgia: The al-Ándalus Project. J Acad Nutr Diet. [Nov 24 Epub ahead of print.] "The results of this study suggest that a daily or almost-daily intake of fruit and vegetables and a moderate intake of fish may be associated with more favorable psychosocial outcomes in women with FM. Conversely, excessive intake of cured meats and sweetened beverages was related to worse scores in optimism and depression outcomes. Future research analyzing dietary patterns as well as intervention studies evaluating the effects of healthy dietary patterns on psychosocial and physical outcomes in individuals with FM are warranted."

Ruiz-Montero PJ, Van Wilgen CP, Segura-Jimenez V et al. 2015. Illness perception and fibromyalgia impact on female patients from Spain and the Netherlands: do cultural differences exist? Rheumatol Int. [May 13 Epub ahead of print.] "Impact of fibromyalgia and negative views of fibromyalgia were higher in Spanish fibromyalgia females, whereas Dutch fibromyalgia females presented higher score of positive beliefs about the controllability of the illness. Psychological interventions which help patients to cope with their illness perception might lead to an improvement of the impact of the disease on fibromyalgia females."

Ruiz Moral R, Rodriguez Salvador J, Perula L et al. 2006.  [Problems and solutions in health care for chronic diseases. A qualitative study with patients and doctors.] Aten Primaria 38(9):483-489. [Spanish]  “To tackle prevalent chronic problems requires, in the view of doctors and patients, important modifications that are related mainly to the kind of relationship between the two, with new clinical responsibilities and certain organizational care delivery features.”  Presently, chronic illness is frustrating to patients and care givers.  Suggestions are given to remedy this.

Rulh A. 2005. Glial cells in the gut.  Neurogastroenterol Motil 17(6):777-790.  [This may have relevance to central sensitization in both FMS and IBS. DJS]

Ruscheweyh R, Sandkuhler J. 2005.  Opioids and central sensitization: II.  Induction and reversal of hyperalgesia. Eur J Pain 9(2):149-152.  “Opioids are powerful analgesics when used to treat acute pain and some forms of chronic pain.  In addition, opioids can preempt some forms of central sensitization.”   This paper reviews evidence that opioids may also induce and also perhaps reverse some forms of central sensitization.

Rush SM, Christensen JC, Johnson CH. 2000.  Biomechanics of the first ray.  Part II: Metatarsus primus varus as a cause of hypermobility.  A three-dimensional kinematic analysis in a cadaver model.  J Foot Ankle Surg 39(2):68-77.  [Tightness of foot muscles, such as that due to myofascial TrPs, could be a major and unrecognized cause of foot hypermobility. DJS]

Russek LN, LaShomb EA, Ware AM et al. 2014. United States Physical Therapists' Knowledge About Joint Hypermobility Syndrome Compared with Fibromyalgia and Rheumatoid Arthritis. Physiother Res Int. [Dec 12 Epub ahead of print.] "Joint hypermobility syndrome (JHS) is one of the most common inherited connective tissue disorders. It causes significant pain and disability for all age groups, ranging from developmental delay among children to widespread chronic pain in adults. Experts in JHS assert that the condition is under-recognized and poorly managed….Cross-sectional, Internet-based survey of randomly selected members of the American Physical Therapy Association and descriptive statistics were used to explore physical therapists' knowledge about JHS, fibromyalgia, juvenile rheumatoid arthritis and adult rheumatoid arthritis, and chi square was used to compare knowledge about the different conditions….The results suggest that many physical therapists in the United States are not familiar with the diagnostic criteria, prevalence or common clinical presentation of JHS."

Russell AL, McCarty MF. 2000.  DL-phenylalanine markedly potentiates opiate analgesia – an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system.  Med Hypotheses 55(4):283-288.

Russell D, Alvarez Gallardo IC, Wilson I et al. 2018. 'Exercise to me is a scary word': perceptions of fatigue, sleep dysfunction, and exercise in people with fibromyalgia syndrome - a focus group study. Rheumatol Int. [Jan 16 Epub ahead of print] "Fatigue, sleep dysfunction, and pain were universally reported by participants. The overarching theme to emerge was a lack of understanding of the condition by others. A huge sense of loss was a major sub-theme and participants felt that they had fundamentally changed since the onset of FMS. Participants reported that they were unable to carry out their normal activities, including physical activity and exercise. The invisibility of FMS was associated with the lack of understanding by others, the sense of loss, and the impact of FMS. People with FMS perceive that there is a lack of understanding of the condition among health care professionals and the wider society. Those with FMS expressed a profound sense of loss of their former 'self'; part of this loss was the ability to engage in normal physical activity and exercise."

Russell IJ. 2011. Future perspectives in generalized musculoskeletal pain syndromes. Best Pract Res Clin Rheumatol. 25(2):321-331. "This article describes contemporary controversies regarding two categories of soft-tissue pain (STP) - chronic widespread pain and fibromyalgia syndrome.... STP classification divides relevant painful conditions into three subgroups, depending on the extent of body involvement (localized, regional and generalized). Fibromyalgia syndrome, in the generalized STP category, is distinguished from other types of chronic widespread pain by virtue of its greater severity. During the past 20 years, the diagnosis of fibromyalgia was based on a research classification (1990 American College of Rheumatology Research Classification Criteria (1990 ACR RCC)) that requires a history of chronic widespread pain and the examination finding of widespread mechanical allodynia. A new approach (2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria (2010 ACR FDC)), validated for clinical use, still requires a history of chronic widespread pain, but the examination is replaced by a historical assessment of co-morbid symptom severity. The populations identified by the two criteria are similar but not identical. Misuse of the new criteria could expand fibromyalgia from 2 to 10% of the general population. Avoidance of the term 'fibromyalgia' could return it to the obscurity from whence it came, leaving a much larger problem in its stead."

Russell IJ. 2003.  Dissecting the Mechanisms of Soft Tissue Pain. J Muscoloskel Pain 11(2):1-2.  In this editorial, Dr. Russell stresses that he believes the importance of identifying subgroups of FMS patients will become much more important in deciding the most effective treatment options.  [I agree with this totally and urge clinicians to take under consideration initiating factors and perpetuating factors when developing FMS treatment regimens.  DJS]

Russell IJ. 2003.  Depression and soft tissue pain.  J Musculoskel Pain 11(1):1-3.  “The old arguments that depression is the cause of low back pain or of pain in patients with fibromyalgia are clearly lame from multiple unsupported parades, but it is fair to say that the resilience of the human spirit becomes less elastic in the presence of chronic pain.”

Russell, IJ. 1999.  Reliability of clinical assessment measures for the classification of myofascial pain syndrome.  J Musculoskel Pain 7(1-2):309-324.

Russell IJ, Holman AJ, Swick TJ et al. 2011. Sodium oxybate reduces pain, fatigue and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study. Pain. [Mar 10 Epub ahead of print]. "These results expand the evidence from previous clinical trials suggesting that SXB is effective and safe in FM. This study expands evidence from previous trials that sodium oxybate provides safe, effective treatment for multiple symptoms experienced by patients with fibromyalgia."


Russell IJ, Larson AA. 2009.  Neurophysiopathogenesis of fibromyalgia syndrome: a unified hypothesis.  Rheum Dis Clin North Am. 35(2):421-435.  “The characteristic presenting complaint of patients with fibromyalgia syndrome (FMS) is chronic widespread allodynia.  Research findings support the view that FMS is an understandable and treatable neuropathophysiologic disorder.  The pain of FMS is often accompanied by one or more other manifestations, such as affective moods, cognitive insecurity, autonomic dysfunction, or irritable bowel or bladder.  Growing evidence suggests that this is a familial disorder with many underlying genetic associations.  New findings from brain imaging and polysomnography imply that FMS may be a disorder of premature neurologic aging.  A conceptual model at the molecular level is proposed to explain many of the observed features of FMS.  The model can also explain anticipated responses to FDA approved pharmacologic therapies.”  [It is unknown at this time as to how much of the irritable bladder and bowel and autonomic dysfunction and other symptoms often attributed to FM may in actuality be due to co-existing TrPs.  This model is very interesting, and as genetic research and epigenetic research unfolds, those of us with FM can look forward to more answers. DJS]

Russo MA , Georgius P, Staats Pires A et al. 2020. Novel immune biomarkers in complex regional pain syndrome. J Neuroimmunol. Jul 21;347:577330." "We investigated serum levels of 29 cytokines and immune-activated kynurenine and tetrahydrobiopterin pathway metabolites in 15 complex regional pain syndrome (CRPS) subjects and 14 healthy controls. Significant reductions in interleukin-37 and tryptophan were found in CRPS subjects, along with positive correlations between kynurenine/tryptophan ratio and TNF-α levels with kinesiophobia, tetrahydrobiopterin levels with McGill pain score, sRAGE, and xanthurenic acid and neopterin levels with depression, anxiety and stress scores. Using machine learning, we identified a set of binary variables, including IL-37 and GM-CSF, capable of distinguishing controls from established CRPS subjects. These results suggest possible involvement of various inflammatory markers in CRPS pathogenesis." [The kynurenine pathway is involved with a subset of FM patients, and it would be interesting to explore this connection as other research has indicated a connection between FM and CRPS. DJS]

Rustoen T, Wahl AK, Hanestad BR et al. 2005.  Age and the experience of chronic pain: differences in health and quality of life among younger, middle-aged and older adults.  Clin J Pain 21(6):513-523.  “The prevalence rates for chronic pain do vary with age and the middle-aged group may be a high-risk group of patients with chronic pain.”  [This may indicate that chronic pain precursors such as individual TrPs and developing initiators of FMS such as lack of restorative sleep are not being diagnosed and adequately treated.  We may be seeing a lack of medical training as a major perpetuating factor of chronic pain. DJS]

Rusu C, Gee ME, Lagace C. 2015. Chronic fatigue syndrome and fibromyalgia in Canada: prevalence and associations with six health status indicators. Health Promot Chronic Dis Prev Can. 35(1):3-11. [Article in English, French] "Co-occurrence of CFS and FM and having other chronic conditions were strongly related to poorer health status and accounted for much of the differences in health status. Understanding factors contributing to improved quality of life in people with CFS and/or FM, particularly in those with both conditions and other comorbidities, may be an important area for future research." Free Article [People are becoming more aware of interactive diagnoses. DJS]

Rusy, L. M., S. A. Harvey and D. J. Beste. 1999. Pediatric fibromyalgia and dizziness: evaluation of vestibular function. J Dev Behav Pediatr 20(4):211-5.

Ryabow S. I. 2002.  Extracellular space volume changes in the cerebral cortex evoked by repetitive peripheral stimulation.  Glia (Suppl 1):S59 [Abstract].

Ryan E, Malboeuf CM, Barnard M et al. 2006.   Cyclooxygenase-2 Inhibition attenuates antibody responses against human papillomavirus-like particles.  J Immunol 177:7811-7819.  Some common over-the counter and other pain medications might weaken vaccines.  Vaccines are give to produce a response of antibodies.  Any COX inhibitor, such as aspirin, Advil, Celebrex, etc., may attenuate this.  In people with compromised immune systems, the effect may be even more pronounced.

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