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."

Lam C, Francio VT, Gustafson K, et al. 2024. Myofascial pain - A major player in musculoskeletal pain. Best Pract Res Clin Rheumatol. 2024 Apr 20:101944. Online ahead of print. "Myofascial pain is a soft tissue pain syndrome with local and referred musculoskeletal pain arising from trigger points. Myofascial pain and myofascial pain syndromes are among some of the most common acute and chronic pain conditions. Myofascial pain can exist independently of other pain generators or can coexist with or is secondary to other acute and chronic painful musculoskeletal conditions. Myofascial pain is most effectively treated with a multimodal treatment plan including injection therapy (known as trigger point injections, physical therapy, postural or ergonomic correction, and treatment of underlying musculoskeletal pain generators."

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."

Lee YH, Song GG. 2024. Association of circulating leptin, growth hormone, and ghrelin with fibromyalgia: A meta-analysis. Growth Horm IGF Res. 2024 Jul 2:77:101606. "This meta-analysis shows that patients with fibromyalgia in Europeans have significantly higher levels of circulating leptin and GH. However, no significant association was found between ghrelin levels and fibromyalgia."

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 J, Si J, Zhao W. 2024. Investigation of the Effect of Tai Chi Training on Depressive Symptoms in Perimenopausal Women on the Basis of Serum Kynurenine Metabolites. Exp Aging Res. 2024 Jul 18:1-19. "Tai Chi training can significantly improve depression symptoms in perimenopausal women. The mechanism of Tai Chi training in improving depression symptoms in perimenopausal women may be achieved by regulating abnormal kynurenine metabolism."

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 LX, Shen MM, Wang QG, Shen W, Yuan Y. 2024. [Clinical study of piriformis syndrome treated with trigger-point acupuncture]. Zhen Ci Yan Jiu. 2024 Sept 25;49(9):957-963. [Chinese]. "The clinical effect of TrP acupuncture is similar to that of glucocorticoid injection on piriformis syndrome in 1 month after treatment. In 2 months after treatment, TrP acupuncture is markedly effective for attenuating pain and the functional impairment of the lower limbs, improving the quality of life and reducing the use of analgesic drugs in comparison with glucocorticoid injection."

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 X, Pan F, Wang Q, et al. 2024. Traditional Chinese rehabilitation exercise (TCRE) for myofascial pain: Current evidence and further challenges. J Pain Res. 2024 Aug 28;17:2801-2810. "Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain."

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 Y, Jin F, Zhou L, et al. 2024. Platelet-derived growth factor receptor-α induces contraction knots and inflammatory pain-like behavior in a rat model of myofascial trigger points. Anesthesiology. 2024 Jul 26. Online ahead of print. "Receptor tyrosine kinases (RTKs) are associated with signal transduction in the central mechanisms of chronic pain but the role of RTKs in the peripheral mechanisms of MTrPs remains unclear…. COL1A1-induced phosphorylation of PDGFR-α and the subsequent activation of the JAK2/STAT3 pathway may induce dysfunctional muscle contraction and increased nociception at MTrPs."

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 21^st 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.

Long Y, Xie X, Wang Y, et al. 2024. Atrophy patterns in hippocampal subregions and their relationship with cognitive function in fibromyalgia patients with mild cognitive impairment. Front Neurosci. 2024 May 23:18:1380121. "These findings suggest that the hippocampal subregions of FM patients might present compensatory mechanisms before cognitive decline occurs."

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.

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."

Lu Y, Wang J, Li L, et al. 2024. The role of voltage-gated calcium channel α2δ-1 in the occurrence and development in myofascial orofacial pain. BMC Oral Health. 2024 May 12;24(1):552. The voltage-gated calcium channel α2δ-1(Cavα2δ-1) may be related to myofascial orofacial pain.

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."

Mackay S, Reber TP, Bausch M, et al. 2024. Concept and location neurons in the human brain provide the 'what' and 'where' in memory formation. Nat Commun. 2024 Sep 10;15(1):7926. "Our brains create new memories by capturing the 'who/what', 'where' and 'when' of everyday experiences…. We investigated this by measuring single neuron activity in the human medial temporal lobe during encoding of item-location associations…. Overall, activation of distinct populations of neurons could directly support the connection of the 'what' and 'where' of episodic memory." [This research may hold some clues including how activation of the temporal lobe of the brain can affect memory. DJS]

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."

Mahmoud NR, Shehab WI, AlAraby AA, et al. 2024. Efficacy of different low-level laser therapy sessions in the management of masseter muscle trigger points. BMC Oral Health. 2024 Sep 26;24(1):1125. "Low-level laser therapy (LLLT) is one of the recent treatment modalities for myofascial pain dysfunction syndrome with trigger points. The objective of the present study was to examine the impact of varying LLLT sessions on the treatment of masseter muscle trigger points…. Increased the number of LLLT sessions reduced the pain improved the MMO (maximum mouth opening), and subsequently improved the quality of life."

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."

Matei D, Traistaru R, Amzolini AM, et al. 2024. A comparative study on the pain threshold experienced by fibromyalgia patients following acute SARS-CoV-2 infection. Life (Basel). 2024 Jul 27;14(8):942. "In conclusion, to control and improve FM pain symptoms, in addition to appropriate medication, we propose paying additional attention to the history of acute SARS-CoV-2 infection and the COVID-19 vaccination status."

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]

Mendonça BTV, Machado V, Silva GG, et al. 2024. Executive functions and functioning in women with fibromyalgia. Arq Neuropsiquiatr. 2024 Sep;82(9):1-9. "Fibromyalgia (FM) is a chronic condition characterized by widespread pain that is associated with sleep, emotional, and cognitive disturbances, including in executive functions (EFs)….The results suggest lower efficiency in processes such as inhibitory control and cognitive flexibility, difficulties in working memory and non-executive processes such as processing speed. Even with pain, anxiety, and depression controlled, some relationships between EFs and functionality were observed, indicating that these symptoms do not fully explain this relationship. We suggest that cognition, particularly EFs, and broader measures of functionality be considered in the evaluation of FM."

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.

Modi DJ, Tuttle JM, Kang S, et al. 2023. Utilizing an ultrasound guided 5-in-1 trigger point and hydrodissection technique for interscapular mid-thoracic myofascial pain: A retrospective review. Interv Pain Med. 2023 Oct 21;2(4):100285.

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."

Montesó-Curto P, Toussaint L, Kueny A, et al. 2024. "Emotional experiences and gender roles of men with fibromyalgia syndrome: a cross-cultural qualitative study. Front Med (Lausanne). 2024 May 20:11:1286729. "This study examined the emotional experience of men with fibromyalgia….Three themes related to feelings/emotions emerged: (1) psychological level; (2) social level; and (3) physical level…. Men often experience negative emotions that are worsened by common misunderstandings and social biases/stigma about their condition…. A proper assessment of emotions when evaluating the global health of men with fibromyalgia as well as the provision of emotional support would improve their mental health and therefore their overall physical health. Emotional management should be incorporated into all treatment protocols for fibromyalgia, especially for men given the gender stigma. Health policies designed by legislators, policymakers, and support agencies must be accompanied by education in gender role concepts to improve the emotions of men with FMS. The mass media will be essential for the disclosure of the emotional suffering of male patients so that society might better understand them."

Monti-Ballano S, Márquez-Gonzalvo S, Lucha-López MO, et al. Effects of dry needling on active myofascial trigger points and pain intensity in tension-type headache: A randomized controlled study. J Pers Med. 2024 Mar 22;14(4):332. "Tension-type headache is the most prevalent type of headache and is commonly associated with myofascial pain syndrome and the presence of active myofascial trigger points. This randomized controlled trial aimed to assess the impact of dry needling on the total number of active trigger points, pain intensity, and perceived clinical change in tension-type headache subjects…. A single dry needling technique was administered at each active trigger point across three sessions…. Dry needling demonstrated positive effects in reducing the number of active trigger points and improving the short-term headache intensity in tension-type headache patients. A single dry needling session applied in the cranio-cervical area resulted in a self-perceived improvement compared to the control subjects."

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]

Namazi G, Chauhan N, Handler S. 2024. Myofascial pelvic pain: the forgotten player in chronic pelvic pain. Curr Opin Obstet Gynecol. 2024 Aug 1;36(4):273-281. "Despite high prevalence of myofascial pelvic pain, screening is not routinely performed by providers. Treatment modalities include pelvic floor physical therapy, pelvic floor trigger point injections with anesthetics or botulinum toxin A and cryotherapy. Other adjunct modalities, such as muscle relaxants and intravaginal benzodiazepines, are used, but data regarding their effectiveness is sparse…. Myofascial pelvic pain is an important, though overlooked component of chronic pelvic pain."

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 HM, Cherry BJ, Zettel-Watson L. 2024. Perceived stress and life stressors in adults with and without fibromyalgia. Biomedicines. 2024 Jun 1;12(6):1233. "Chronic medical conditions (i.e., chronic widespread pain) may contribute to accelerated/accentuated aging, such that middle-aged individuals with comorbidities may actually show increased declines in physical, cognitive, and mental health compared to normal aging adults…. Significant associations were found between perceived stress and life stressors in all participants. In addition, those with fibromyalgia were significantly more likely to report higher levels of stress above standardized scores on both the Perceived Stress Scale and the Social Readjustment Rating Scale. Finally, depressive symptoms played a more significant role than fibromyalgia status in predicting life stressors."

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.