Pain Medicine

Fibromyalgia

Fibromyalgia · M79.7

Fibromyalgia is a chronic widespread pain condition associated with central sensitization and autonomic nervous system dysfunction, accompanied by fatigue, sleep disturbances, and cognitive difficulties.

2026-03-28

At a Glance

Fibromyalgia affects 2-4% of the population and is characterized by widespread musculoskeletal pain persisting for more than 3 months. Central sensitization amplifies pain signals in the CNS, while autonomic dysfunction manifests as reduced HRV and sympathetic hyperactivity. The 2016 revised criteria require a widespread pain index (WPI) and symptom severity scale (SSS) score above threshold. First-line treatments include duloxetine, pregabalin, and milnacipran, combined with aerobic exercise and cognitive behavioral therapy.

Definition and Overview

Fibromyalgia is a chronic pain syndrome characterized by widespread musculoskeletal pain persisting for more than 3 months, accompanied by fatigue, sleep disturbance, and cognitive impairment. The hallmark is pain occurring without tissue damage or clear inflammatory findings, with central sensitization as the core pathophysiological mechanism [2].

Global prevalence is estimated at 2-4%, with women affected approximately 7 times more than men [1]. Onset typically occurs between ages 20-55, and co-occurrence with rheumatoid arthritis is not uncommon.

Causes and Mechanisms

Central Sensitization

The most important mechanism of fibromyalgia is central sensitization. Pain processing circuits in the brain and spinal cord become hypersensitized, producing excessive pain responses to normally non-painful stimuli [2]. Functional MRI studies show significantly higher activation of pain processing brain regions in fibromyalgia patients compared to healthy individuals.

Autonomic Dysfunction

Many fibromyalgia patients exhibit decreased heart rate variability (HRV), sympathetic dominance, and reduced parasympathetic activity [3]. Sympathetic hyperactivation reduces muscle blood flow and lowers pain thresholds, creating a pain vicious cycle.

Genetic and Environmental Factors

Genetic polymorphisms related to serotonin, dopamine, and norepinephrine have been associated with fibromyalgia risk [5]. Physical trauma, emotional trauma, viral infections, sleep disorders, and chronic stress serve as triggering factors.

Symptoms

Primary Symptoms

Core symptoms of fibromyalgia include:

  • Widespread pain: musculoskeletal pain affecting both sides, upper and lower body
  • Tenderness: excessive pain response when pressing specific areas of the neck, shoulders, chest, back, and extremities
  • Fatigue: chronic fatigue unrelieved by sleep
  • Sleep disturbance: difficulty falling asleep, frequent awakening, non-restorative sleep
  • Cognitive impairment (fibro fog): decreased concentration, memory decline, slowed thinking

Associated Symptoms

Headache, irritable bowel syndrome, bladder hypersensitivity, restless legs syndrome, and depression/anxiety commonly co-occur. Research shows depressive disorder accompanies approximately 30-50% of fibromyalgia patients [2].

Diagnosis

2010 ACR Diagnostic Criteria

The American College of Rheumatology (ACR) 2010 criteria use the Widespread Pain Index (WPI) and Symptom Severity Scale (SS) [1].

  • WPI >= 7 + SS >= 5, or WPI 3-6 + SS >= 9
  • Symptoms persist at a similar level for 3 or more months
  • No other condition explains the pain

Differential Diagnosis

Differentiation from hypothyroidism, rheumatoid arthritis, systemic lupus erythematosus, small fiber neuropathy, and chronic fatigue syndrome is necessary. Basic blood tests (CBC, ESR, CRP, thyroid function) rule out organic causes.

Treatment

Non-pharmacological Treatment

Aerobic exercise has the strongest evidence for improving pain, fatigue, and quality of life in fibromyalgia [3]. Low-intensity exercises such as aquatic exercise, walking, yoga, and tai chi performed at least 3 times per week are effective.

Cognitive behavioral therapy (CBT) significantly reduces pain intensity and functional disability by changing pain perception and coping strategies [3].

Pharmacotherapy

FDA-approved medications for fibromyalgia include:

  • Pregabalin: calcium channel modulator that inhibits central sensory signal transmission
  • Duloxetine: serotonin-norepinephrine reuptake inhibitor (SNRI)
  • Milnacipran: SNRI-class medication

Tricyclic antidepressants (amitriptyline) are effective for sleep improvement and pain reduction at low doses [2].

Autonomic Neuromodulation

In cases with sympathetic hyperactivation and reduced HRV, stellate ganglion block and transcranial magnetic stimulation (TMS) may be used as adjunctive autonomic neuromodulation therapy for pain threshold improvement and sleep restoration.

Lifestyle Management

  • Sleep hygiene: maintain regular sleep/wake times, limit caffeine, improve sleep environment
  • Stress management: diaphragmatic breathing, mindfulness meditation, relaxation training
  • Energy management (pacing): balance activity and rest to prevent post-exertional malaise
  • Diet: anti-inflammatory diet (Mediterranean style), adequate hydration

Frequently Asked Questions

FAQ content is being prepared.

References

  1. [1] Wolfe F, Clauw DJ, Fitzcharles MA, Goldenberg DL, Katz RS, Mease P, Russell AS, Russell IJ, Winfield JB, Yunus MB (2010). "The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity." Arthritis Care & Research, 62: 600-610. DOI PubMed
  2. [2] Clauw DJ (2014). "Fibromyalgia: a clinical review." JAMA, 311: 1547-1555. DOI PubMed
  3. [3] Häuser W, Ablin J, Fitzcharles MA, Littlejohn G, Lucena M, Usui C, Walitt B (2015). "Fibromyalgia." Nature Reviews Disease Primers, 1: 15022. DOI PubMed
  4. [4] Meeus M, Nijs J, Hermans L, Goubert D, Calders P (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 Opinion on Therapeutic Targets, 17: 1081-1089. DOI PubMed
  5. [5] Ablin JN, Buskila D (2015). "Update on the genetics of the fibromyalgia syndrome." Best Practice & Research Clinical Rheumatology, 29: 20-28. DOI PubMed
fibromyalgiachronic paincentral sensitizationautonomic dysfunctionwidespread painfatigue

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