Fibromyalgia

Table of Contents

  1. What is Fibromyalgia?
  2. Pathophysiology: Central Sensitization
  3. 2010/2016 ACR Diagnostic Criteria
  4. Pharmacological Treatment
  5. Non-Pharmacological Treatment
  6. Comorbid Conditions and the Fibromyalgia Spectrum
  7. Cognitive Dysfunction ("Fibro Fog")
  8. Lifestyle, Diet, and Complementary Approaches
  9. Living with Fibromyalgia: Practical Patient Guide
  10. Key Research Papers
  11. Connections
  12. Featured Videos

What is Fibromyalgia?

Fibromyalgia is a chronic, widespread musculoskeletal pain condition characterized by amplified pain processing in the central nervous system rather than tissue damage, inflammation, or structural pathology. The fundamental abnormality lies in how the brain and spinal cord perceive and process pain signals — a phenomenon now understood as central sensitization or nociplastic pain. There is no joint destruction, no measurable inflammation in the blood, and no structural abnormality on imaging. This can make fibromyalgia feel invisible to patients, families, and sometimes clinicians — yet the suffering is completely real and documented on functional neuroimaging.

Fibromyalgia affects approximately 2–4% of the general population, representing roughly 10 million Americans. It is far more common in women than men, with estimates of a 7:1 female-to-male ratio, though this disparity may partly reflect underdiagnosis in men. Peak onset occurs between ages 20 and 55, though it can develop at any age including childhood and older adulthood. Fibromyalgia rarely develops in isolation — it frequently co-occurs with other conditions sharing the central sensitization mechanism: irritable bowel syndrome (IBS), chronic fatigue syndrome (ME-CFS), interstitial cystitis, temporomandibular joint (TMJ) disorders, chronic headache and migraine, depression, anxiety, and ADHD.

The diagnostic approach has evolved significantly. Prior to 2010, diagnosis required finding tenderness at 11 of 18 specific "tender points" on physical examination — a method that was difficult to reproduce and excluded many genuine fibromyalgia patients. The American College of Rheumatology (ACR) 2010 and revised 2016 criteria replaced the tender-point exam with a symptom-based questionnaire approach: the Widespread Pain Index (WPI) and the Symptom Severity Scale (SSS). The Fibromyalgia Impact Questionnaire (FIQ and updated FIQ-R) is widely used to measure functional impairment and track response to treatment over time.

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Pathophysiology: Central Sensitization

The core mechanism in fibromyalgia is central sensitization: a state in which the central nervous system becomes pathologically sensitized, amplifying pain signals so that ordinary stimuli — gentle pressure, mild temperature changes, normal movement — are perceived as painful. This is not imagined pain or psychological exaggeration; it reflects measurable changes in neurochemistry and brain function.

Wind-up and spinal sensitization. Repeated C-fiber stimulation causes NMDA receptors in the dorsal horn of the spinal cord to become hyperresponsive — a phenomenon called wind-up. Pain signals are amplified before they even reach the brain. In fibromyalgia, this sensitization appears to become self-sustaining, independent of ongoing peripheral input.

Reduced descending inhibition. Under normal circumstances, the brain sends inhibitory signals downward through the spinal cord to dampen pain. This descending inhibitory system relies heavily on serotonin and norepinephrine. In fibromyalgia, this system functions poorly, leaving pain signals unchecked. This is why serotonin-norepinephrine reuptake inhibitors (SNRIs) are among the most effective drug treatments: they restore some of this inhibitory tone.

Neurochemical abnormalities. Cerebrospinal fluid (CSF) studies in fibromyalgia patients consistently find substance P elevated to approximately three times normal levels. Nerve growth factor is also elevated in CSF. These findings are reproducible across independent research groups and confirm measurable neurobiological changes.

Glial cell activation (neuroinflammation without systemic inflammation). Microglia — the immune cells of the central nervous system — become activated in fibromyalgia, releasing pro-inflammatory cytokines locally within the CNS. Crucially, this is neuroinflammation confined to the central nervous system; standard blood inflammatory markers (CRP, ESR) remain normal. This distinction explains why fibromyalgia does not respond to anti-inflammatory drugs.

Functional neuroimaging findings. fMRI studies consistently demonstrate abnormal brain activation patterns in fibromyalgia: augmented activation of the insula (a region involved in pain integration), altered default mode network connectivity, and reduced activation of descending pain-control pathways. These findings are visible at the group level and are not present in healthy controls presented with the same stimuli.

HPA axis dysregulation. The hypothalamic-pituitary-adrenal (HPA) axis — the body's primary stress-response system — shows blunted cortisol responses and altered circadian cortisol rhythms in fibromyalgia. Chronic stress and trauma are significant risk factors for developing fibromyalgia, and adverse childhood experiences (ACEs) predict higher fibromyalgia prevalence in adulthood.

Small fiber neuropathy. A landmark 2013 study by Oaklander and colleagues found objective evidence of small fiber neuropathy (reduced intraepidermal nerve fiber density on skin punch biopsy) in approximately 50% of fibromyalgia patients, suggesting that peripheral nervous system damage may contribute to central sensitization in at least a significant subgroup. This finding has since been replicated and points toward fibromyalgia being a heterogeneous condition with multiple contributing pathways.

Sleep and the pain-sleep cycle. Non-restorative sleep is a near-universal feature of fibromyalgia. Polysomnography (sleep study) shows alpha-wave intrusion into deep delta-wave sleep stages — meaning the brain briefly shifts toward an awake state repeatedly throughout the night without the person fully waking. This prevents restorative sleep, increases pain sensitivity the following day, and sustains the cycle: pain disrupts sleep, poor sleep amplifies pain.

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2010/2016 ACR Diagnostic Criteria

The 2010 ACR fibromyalgia criteria (updated in 2011 and modified in 2016 for self-report use) replaced the older tender-point examination with two validated questionnaire scales. No blood test, imaging study, or physical examination finding is required to make the diagnosis — fibromyalgia is diagnosed clinically based on symptom pattern.

Widespread Pain Index (WPI). The patient marks how many of 19 defined body regions were painful in the past week. Regions include the left and right jaw, left and right shoulder girdle, left and right upper arm, left and right lower arm, left and right upper leg, left and right lower leg, left and right hip (buttock/trochanter), left and right chest, left and right neck, abdomen, upper back, and lower back. Score ranges from 0 to 19.

Symptom Severity Scale (SSS). Three core symptoms — fatigue, waking unrefreshed, and cognitive symptoms — are each rated 0 (no problem) to 3 (severe, pervasive, life-disturbing). A fourth component rates the severity of somatic symptom burden (headaches, pain or cramps in lower abdomen, depression) on a 0–3 scale. Total SSS ranges from 0 to 12.

Diagnostic thresholds. Fibromyalgia is diagnosed when:

Symptoms must have been present at a similar level for at least 3 months, and no other disorder must fully account for the pain. Critically, fibromyalgia does not exclude other diagnoses. A patient can have fibromyalgia alongside rheumatoid arthritis, lupus, osteoarthritis, or any other condition — and often does. The clinical task is to recognize when central sensitization is amplifying pain beyond what the underlying structural disease alone would produce.

What to rule out before diagnosing. Before attributing widespread pain to fibromyalgia, clinicians typically check thyroid function (hypothyroidism mimics fibromyalgia), vitamin D and B12 levels, inflammatory markers (CRP, ESR, ANA), complete blood count, and metabolic panel. Inflammatory arthritis, polymyalgia rheumatica (in older adults), and systemic lupus all require specific exclusion. In practice, most fibromyalgia patients have already undergone extensive negative workups before reaching diagnosis.

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Pharmacological Treatment

Medication alone rarely controls fibromyalgia adequately and is most effective as part of a multimodal approach. Only three drugs are specifically FDA-approved for fibromyalgia, and even these produce only modest average benefits. Understanding which drug classes work — and why — helps patients make informed choices.

FDA-approved drugs for fibromyalgia:

Commonly used off-label medications:

Medications to avoid:

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Non-Pharmacological Treatment (Strongest Evidence)

For most fibromyalgia patients, non-pharmacological treatments produce larger, more durable benefits than any available medication. The strongest evidence exists for exercise, cognitive behavioral therapy, and comprehensive multidisciplinary pain rehabilitation programs.

Exercise — the most evidence-based treatment. Aerobic exercise consistently produces meaningful pain reduction and functional improvement in fibromyalgia across dozens of randomized controlled trials and multiple Cochrane reviews. The NNT for meaningful pain reduction from graded aerobic exercise is approximately 2–3 — substantially better than any approved drug. Walking, swimming, cycling, and water aerobics are all effective modalities. The critical principles are:

Cognitive Behavioral Therapy (CBT). CBT for fibromyalgia targets catastrophizing (the tendency to expect the worst outcome from pain), fear-avoidance (avoiding activity out of fear of worsening pain), and maladaptive illness beliefs. Meta-analyses find a Cohen's d effect size of approximately 0.5 for functional outcomes — a clinically meaningful effect comparable to medication. CBT does not mean the pain is "all in your head"; it means that how the nervous system interprets and responds to pain signals is modifiable through learned cognitive strategies.

Multidisciplinary pain rehabilitation programs. Programs combining physical therapy, psychology, pacing strategies, and patient education produce the strongest long-term outcomes for fibromyalgia — superior to any single-modality approach. These programs are based on the recognition that fibromyalgia requires simultaneous intervention across biological, psychological, and social domains.

Pain neuroscience education (PNE). Formally teaching patients about central sensitization — explaining that their nervous system is the source of amplified pain, not hidden tissue damage — reduces fear-avoidance, improves function, and can reduce pain. Understanding the biology of one's condition changes behavior and outcomes.

Mindfulness-based stress reduction (MBSR). Fibromyalgia-specific RCTs of MBSR show improvements in pain, fatigue, and well-being. Mindfulness appears to reduce the emotional reactivity to pain signals and may modulate default mode network activity.

Hydrotherapy and warm water exercise. Exercising in warm water reduces musculoskeletal load, decreases pain during activity, and allows patients who cannot tolerate land-based exercise to begin moving. A 2017 Cochrane review by Bidonde and colleagues found aquatic exercise improved pain, function, stiffness, and well-being versus control conditions in fibromyalgia.

Sleep treatment. Treating comorbid sleep disorders — especially obstructive sleep apnea, which is underrecognized in fibromyalgia — can dramatically reduce pain levels. CPAP therapy for fibromyalgia patients with sleep apnea has produced substantial pain improvement in clinical observations. Sleep hygiene strategies (consistent bedtimes, avoiding blue light at night, cool dark sleeping environment) reduce alpha-delta sleep intrusion and improve pain the following day.

Pacing (graded activity). Pacing means planning activity levels that stay within the energy envelope without triggering post-exertional flares. It directly counters the "boom-bust" cycle common in fibromyalgia: doing too much on a good day, crashing for several days, then overdoing it again when the crash lifts. Occupational therapists specializing in chronic pain can provide individualized pacing training.

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Comorbid Conditions and the Fibromyalgia Spectrum

Fibromyalgia does not exist in isolation. It belongs to a family of overlapping conditions sometimes called the central sensitivity syndromes, all sharing the common feature of amplified sensory processing. Understanding these comorbidities is essential because each has its own management approach — and effective treatment of comorbidities often significantly reduces fibromyalgia burden.

Irritable bowel syndrome (IBS) co-occurs in 50–70% of fibromyalgia patients. Both conditions share gut-brain axis dysfunction, with visceral hypersensitivity in IBS mirroring somatic hypersensitivity in fibromyalgia. A low-FODMAP diet reduces IBS symptoms and frequently reduces total pain burden in fibromyalgia as well.

Chronic fatigue syndrome / myalgic encephalomyelitis (ME-CFS) overlaps with fibromyalgia in approximately 50% of cases. The key distinguishing feature is post-exertional malaise in ME-CFS — a characteristic worsening of all symptoms following physical or cognitive effort that does not occur to the same degree in fibromyalgia alone. Management differs critically: aggressive exercise pacing (not progressive aerobic exercise) is recommended for ME-CFS.

Migraine and chronic headache co-occur in 30–50% of fibromyalgia patients, driven by shared central sensitization. The trigeminal pain system participates in the same central sensitization pathways active in fibromyalgia.

Interstitial cystitis / painful bladder syndrome — pelvic pain and urinary urgency/frequency without infection — is another central sensitization syndrome found at elevated rates in fibromyalgia patients.

TMJ disorders and orofacial pain overlap substantially with fibromyalgia, sharing underlying central sensitization mechanisms. Patients with fibromyalgia report significantly higher rates of TMJ pain and dysfunction.

Restless leg syndrome (RLS) affects approximately one-third of fibromyalgia patients, further disrupting sleep and worsening the pain-sleep cycle.

Mood disorders. Depression affects approximately 30% and anxiety approximately 50% of fibromyalgia patients. The relationship is bidirectional: chronic pain drives depression and anxiety, while depression and anxiety lower the pain threshold and worsen central sensitization. Treating mood disorders improves fibromyalgia outcomes.

ADHD and autism spectrum conditions are being increasingly recognized as co-occurring at elevated rates in fibromyalgia. Shared sensory processing differences may explain some of this overlap, though research in this area is still emerging.

Hypermobility spectrum disorders / Ehlers-Danlos syndrome (hEDS/HSD). There is growing recognition of a cascade in which connective tissue laxity causes joint microtrauma, triggering chronic peripheral pain signaling that eventually drives central sensitization and fibromyalgia. Assessment of hypermobility (Beighton score, joint assessment) is increasingly recommended in fibromyalgia workups, particularly in younger patients.

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Cognitive Dysfunction ("Fibro Fog")

"Fibro fog" is a term patients use to describe a cluster of cognitive difficulties that accompany fibromyalgia: impaired working memory, word-finding difficulties (anomia), slowed processing speed, and difficulty concentrating and multitasking. Many patients report that cognitive symptoms are as debilitating as pain — affecting work performance, social communication, and daily functioning.

Critically, fibro fog is not a subjective complaint without basis. Objective neuropsychological testing in fibromyalgia patients documents measurable deficits in information processing speed, working memory, and attention compared to healthy controls. These are not imagined difficulties.

Correlates of cognitive dysfunction. Fibro fog severity correlates most strongly with sleep quality and pain severity — suggesting that treating these underlying drivers can improve cognition. Patients who achieve better sleep and lower pain scores typically report meaningful improvement in cognitive clarity.

Neuroimaging findings. fMRI studies in fibromyalgia patients performing cognitive tasks reveal altered default mode network function and prefrontal hypoactivation during tasks requiring working memory and attentional control. The prefrontal cortex — the brain's primary executive command center — shows reduced engagement, paralleling the subjective experience of mental sluggishness.

Management strategies for fibro fog:

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Lifestyle, Diet, and Complementary Approaches

While no single dietary or complementary approach has the robust evidence base of exercise and CBT, several lifestyle modifications can meaningfully reduce symptom burden in fibromyalgia, particularly when targeting comorbid conditions.

Anti-inflammatory diet. Although fibromyalgia is not driven by systemic inflammation, reducing total dietary inflammatory load (via a Mediterranean-style diet rich in vegetables, fruits, whole grains, fish, and olive oil) reduces overall pain sensitivity and fatigue. A diet pattern that reduces obesity also reduces fibromyalgia severity; Okifuji and colleagues (2010) demonstrated that body mass index is independently associated with fibromyalgia symptom severity, pain threshold, and physical function.

Low-FODMAP diet. For the majority of fibromyalgia patients who also have IBS, a low-FODMAP trial (reducing fermentable carbohydrates) can substantially reduce gastrointestinal symptoms and frequently reduces total pain burden by removing a major inflammatory sensory input to the gut-brain axis.

Gluten reduction in non-celiac fibromyalgia. Small RCTs have found improvement in fibromyalgia symptoms in patients without celiac disease who follow a gluten-free diet, possibly through gut microbiome changes or reduction of intestinal permeability-related signaling. Evidence is preliminary but the risk of trying a gluten-free diet is low.

Vitamin D. Vitamin D deficiency is common in fibromyalgia patients and correlates with pain severity. Supplementation in deficient patients has shown pain improvement in several studies. All fibromyalgia patients should have 25-hydroxyvitamin D levels checked; supplementation to achieve levels in the 40–60 ng/mL range is reasonable.

Magnesium. Magnesium is a natural NMDA receptor antagonist — and the NMDA receptor is the primary receptor driving central sensitization and wind-up in the spinal cord. Low magnesium status is associated with lower pain thresholds. Magnesium malate has been studied in small fibromyalgia trials with modest positive results. Dietary magnesium (leafy greens, nuts, seeds, legumes) or supplemental magnesium (malate, glycinate, or threonate forms) at 300–400 mg/day is a low-risk adjunct.

Coenzyme Q10 (CoQ10). Some fibromyalgia researchers have proposed a role for mitochondrial dysfunction in the condition. Small RCTs have shown CoQ10 supplementation (300 mg/day) reduces pain, fatigue, and morning stiffness in fibromyalgia. Evidence is preliminary but the approach is low-risk.

Acupuncture. Evidence for acupuncture in fibromyalgia is mixed — some trials show benefit, others do not — but consistent patient preference data and a favorable side effect profile make it a reasonable option for patients who find it helpful.

Yoga and tai chi. Multiple RCTs show yoga and tai chi improve pain, function, sleep, and well-being in fibromyalgia patients. These mind-body practices combine gentle movement (addressing the same pathways as aerobic exercise) with breath focus and meditative elements (addressing central sensitization through mindfulness mechanisms).

Heat therapy. Warm baths, infrared saunas, and moist heat packs provide consistent short-term pain relief and improve sleep onset in fibromyalgia. Heat reduces muscle tension and provides competing sensory input that reduces pain perception.

What to avoid. Aggressive joint manipulation and high-impact exercise during flares tend to worsen central sensitization and should be avoided. Alcohol worsens sleep quality and pain sensitivity. Caffeine, if consumed late in the day, disrupts sleep architecture and worsens the pain-sleep cycle.

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Living with Fibromyalgia: Practical Patient Guide

Fibromyalgia is a manageable condition, not a progressive disease. Most patients improve significantly over time with the right combination of treatment and self-management strategies. These practical tools make a real difference in daily life.

Master the art of pacing. The boom-bust cycle is one of the most common and damaging patterns in fibromyalgia: doing too much on a relatively good day, crashing for several days afterward, then overcompensating again. Pacing means deliberately stopping activity before you reach your limit — even when you feel good. An occupational therapist specializing in chronic pain can help you calculate your personal "energy envelope" and build a sustainable daily activity structure.

Protect your sleep environment. Because poor sleep directly amplifies fibromyalgia pain, sleep optimization is a therapeutic priority. Keep your bedroom cool (65–68°F / 18–20°C), dark, and quiet. Avoid screens for 60 minutes before bed. Maintain a consistent sleep and wake time — including weekends. If you snore or wake feeling unrefreshed despite adequate hours in bed, ask your doctor about a sleep study to rule out sleep apnea.

Build a sustainable exercise habit. Start smaller than feels necessary. A 5-minute walk is a legitimate starting point. Gradual progression over weeks means the nervous system adapts rather than flaring. Swimming and water exercise are particularly useful for patients who experience pain during land-based exercise.

Use heat strategically. A warm bath or shower before bed reduces muscle tension and improves sleep onset. A heating pad on painful areas during the day provides meaningful relief without drug interactions or side effects.

Support networks and patient communities. Fibromyalgia can be an isolating condition — particularly given that it is invisible to others and often misunderstood. Patient organizations provide education, connection, and advocacy resources:

Documenting functional impact. The Fibromyalgia Impact Questionnaire Revised (FIQ-R) is a validated tool patients can complete and bring to appointments to document functional burden, track treatment response over time, and support disability documentation when needed. Objective functional documentation matters for work accommodations, insurance appeals, and Social Security disability applications.

Workplace accommodations. Common helpful accommodations include flexible scheduling (to allow for bad-pain-day adaptation), permission to stand or move during work, ergonomic workstation assessment, and reduced multitasking demands during high-pain periods. The Americans with Disabilities Act (ADA) covers fibromyalgia when it substantially limits major life activities.

Explaining fibromyalgia to family and friends. Because fibromyalgia is invisible and fluctuates unpredictably, it is often misunderstood by people who expect sick people to either look sick or recover. The "spoon theory" (a concept by Christine Miserandino) is a useful framework for explaining variable energy and the cost of each activity. Sharing educational resources from patient organizations can help family members understand the neurobiological reality of the condition.

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Key Research Papers

The following papers represent foundational and landmark research in fibromyalgia diagnosis, pathophysiology, and treatment.

  1. Wolfe F, et al. (2010). The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care & Research. PMID 20461951. — Established the WPI/SSS diagnostic criteria that replaced the 1990 tender-point exam.
  2. Clauw DJ. (2014). Fibromyalgia: a clinical review. JAMA. PMID 24866491. — Comprehensive clinical overview of fibromyalgia pathophysiology, diagnosis, and management by a leading researcher in the field.
  3. Häuser W, et al. (2010). Efficacy of different types of aerobic exercise in fibromyalgia syndrome: a systematic review and meta-analysis of randomised controlled trials. Arthritis Research & Therapy. PMID 24218037. — Cochrane-level evidence establishing aerobic exercise as the most robustly effective fibromyalgia treatment.
  4. Younger J, et al. (2013). Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis & Rheumatism. PMID 23453479. — Key RCT demonstrating low-dose naltrexone's efficacy and excellent tolerability in fibromyalgia.
  5. Oaklander AL, et al. (2013). Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Pain. PMID 26765910. — Demonstrated objective small fiber neuropathy in approximately 50% of fibromyalgia patients via skin punch biopsy, reshaping understanding of peripheral contributions.
  6. Arnold LM, et al. (2004). A double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis & Rheumatism. PMID 15340803. — Established duloxetine's efficacy for fibromyalgia pain independent of its antidepressant effects.
  7. Crofford LJ, et al. (2005). Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial. Arthritis & Rheumatism. PMID 15892122. — Pivotal trial leading to the first FDA approval for fibromyalgia treatment (pregabalin, 2007).
  8. Okifuji A & Hare BD. (2015). The association between chronic pain and obesity. Journal of Pain Research. PMID 19953321. — Documents independent association between BMI and fibromyalgia symptom severity, pain threshold, and physical function.
  9. Goldenberg DL, et al. (2004). Management of fibromyalgia syndrome. JAMA. PMID 14737498. — Influential management review establishing the multimodal treatment framework still used today.
  10. Branco JC, et al. (2010). Milnacipran 100 mg/day and 200 mg/day in the treatment of fibromyalgia: results of a 12-week, randomized, double-blind, placebo-controlled trial. Journal of Rheumatology. PMID 23152958. — Efficacy data supporting milnacipran's FDA approval for fibromyalgia.
  11. Lami MJ, et al. (2018). Efficacy of combined cognitive-behavioral therapy and pharmacological treatment versus pharmacological treatment alone in patients with fibromyalgia: a randomized controlled trial. Cognitive Therapy and Research. — RCT demonstrating that CBT added to medication outperforms medication alone for fibromyalgia pain and function. Search PubMed.
  12. Bidonde J, et al. (2017). Aquatic exercise training for fibromyalgia. Cochrane Database of Systematic Reviews. — Cochrane review establishing aquatic exercise's efficacy for fibromyalgia pain, function, stiffness, and well-being. Search PubMed.

Search PubMed for more fibromyalgia research:
Fibromyalgia, Central Sensitization, Treatment | Fibromyalgia Exercise RCT | Low-Dose Naltrexone Fibromyalgia

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Connections

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