Overview

Fibromyalgia is a chronic, nociplastic pain condition characterised by widespread pain with prominent fatigue, sleep disturbance, and cognitive symptoms, reflecting altered central pain processing rather than tissue injury. Global prevalence is ~2–4%, higher in women, ages 20–60, and in those with mood/sleep disorders, obesity, low socioeconomic status, and comorbid rheumatic disease. Major complications include functional impairment, work disability, polypharmacy, and elevated risks of depression and suicidality; timely, multimodal, non-pharmacological care improves outcomes [2,5,15]. 

Classification

Chronic pain is now categorised according to the International Classification of Diseases, 11th Revision (ICD-11) into two main groups: chronic primary pain and chronic secondary pain. This classification helps distinguish pain as a disease in itself versus pain as a symptom of another condition.

Chronic Primary Pain

• Definition: Pain that persists for ≥3 months and is not better explained by another condition. It is considered a disease in its own right, often associated with emotional distress or functional disability.
• Examples
  • Chronic widespread pain (CWP)
  • Fibromyalgia
  • Complex regional pain syndrome (CRPS)
  • Chronic primary headache
  • Chronic primary visceral pain (e.g., irritable bowel syndrome)
  • Chronic primary musculoskeletal pain (e.g., non-specific low back pain)

Chronic Secondary Pain

• Definition: Pain that arises as a symptom secondary to an underlying disease.
• Subtypes:
  • Chronic cancer-related pain
  • Chronic postsurgical or post-traumatic pain
  • Chronic neuropathic pain (e.g., diabetic neuropathy)
  • Chronic secondary musculoskeletal pain (e.g., due to osteoarthritis or rheumatoid arthritis)
  • Chronic secondary visceral pain (e.g., due to endometriosis)
  • Chronic secondary headache or orofacial pain

Anatomy & Physiology 

• Ascending nociceptive pathways: peripheral A-delta/C fibres → dorsal horn → spinothalamic/limbic projections → thalamus → primary/secondary somatosensory cortices, insula, ACC.
• Descending modulation: periaqueductal grey–rostral ventromedial medulla pathways inhibit/facilitate dorsal horn transmission via serotonin, noradrenaline, endogenous opioids.
• Sleep–pain interface: slow-wave sleep maintains descending inhibition; sleep loss augments temporal summation.
• Autonomic–HPA axis: sympathetic arousal and cortisol rhythms modulate pain thresholds and fatigue.

Aetiology and Risk Factors

Aetiology (multifactorial, biopsychosocial)

• CNS hyperexcitability and impaired descending inhibition (nociplastic pain) 
• Neuroinflammation/glial activation in pain networks (PET evidence)
• Small-fibre pathology in a subset (reduced intra-epidermal nerve fibre density)
• Dysregulated stress systems: autonomic (sympathetic overactivity) and HPA axis alterations
• Genetic/familial susceptibility with environmental triggers (infection, trauma, major stress)

Risk factors

• Female sex, middle age
• Insomnia/sleep apnoea
• Depression/anxiety
• Obesity/inactivity
• Adverse childhood experiences (PTSD)
• Catastrophizing
• Low socioeconomic status
• Comorbid rheumatic or pain disorders
• Viral illness or physical trauma as precipitant

Pathophysiology 

• Predisposition (genes, sex hormones, early adversity) → heightened pain gain setting.
• Trigger (infection, trauma, psychosocial stress, poor sleep) → increased peripheral input + stress reactivity.
• CNS changes: augmented temporal summation, impaired conditioned pain modulation, altered connectivity/chemistry in insula–ACC–DMN; glial activation and pro-inflammatory signalling sustain hyperexcitability
• Systemic correlates: autonomic dysregulation (orthostatic symptoms), HPA rhythm changes, microglial cytokines, altered neurotransmitters (↓NA/5-HT; ↑glutamate)
• Clinical expression: widespread pain, sensory hypersensitivity, fatigue, sleep/cognitive symptoms; in a subset, small-fibre pathology contributes to dysaesthesias [9].

Clinical Manifestations

• Pain: chronic (≥3 months) widespread or multisite pain, often migratory; hyperalgesia/allodynia on light pressure (e.g., trapezius, lateral epicondyle, gluteal).
• Somatic symptoms: morning stiffness, paraesthesias, headaches/migraine, functional bowel/bladder symptoms, TMJ pain.
• Fatigue and post-exertional symptom exacerbation; non-restorative sleep, insomnia; cognitive “fibro-fog” (attention/processing speed).
• Mood: anxiety/depression common; heightened stress sensitivity.
• Autonomic: orthostatic intolerance, palpitations, thermodysregulation; sicca-like symptoms.

Clinical Examination

• Normal joints and neurology
• Tenderness to ~4 kg thumb pressure at multiple sites
• Normal ROM
• No synovitis 
• No objective weakness.
  

Diagnosis

• 2016 ACR Diagnostic Criteria:
  • WPI ≥7 and SSS ≥5 or WPI 4–6 and SSS ≥9.
  • Generalised pain in ≥4 of 5 regions (jaw, chest, abdomen excluded).
  • Symptoms present at a similar level ≥3 months.
  • Diagnosis valid irrespective of other illnesses if criteria met.
    
• AAPT 2019 criteria (alternative research/clinical framework): multisite pain (≥6/9 regions), fatigue and sleep/cognitive symptoms, ≥3 months, not better explained by another disorder.
  
• Investigations (rule-out/minimise over-testing): FBC, TSH, CRP/ESR, CMP ± CK, coeliac serology if GI symptoms; screen for OSA when indicated; consider B12, ferritin when fatigued; autoimmune tests only if clinical suspicion of CTD
  
• Differential Diagnosis
  • Hypothyroidism (TSH ↑, cold intolerance).
  • Inflammatory rheumatic disease (objective synovitis, raised CRP/ESR, erosions).
  • Myopathies (objective weakness, CK ↑).
  • Small fibre neuropathy (length-dependent burning pain, reduced IENFD on biopsy).
  • Chronic fatigue syndrome/ME (post-exertional malaise predominates; overlapping but distinct).
    

Treatment

• Conservative measures 
  • Education
  • Graded aerobic/strength exercise (land or aquatic)
  • CBT or psychologically informed therapy
  • Prioritise sleep optimisation 
  • Self-management (pacing, goal setting)
  • Adjuncts (individualise): meditative movement (tai chi, yoga), mindfulness-based stress reduction, acupuncture; treat comorbidities (depression, OSA, obesity) to improve global outcomes
    
• Pharmacological (for severe pain/sleep disturbance after core care)
  • SNRIs: duloxetine or milnacipran (pain, function).
  • Pregabalin (sleep, pain); gabapentin less certain.
  • Low-dose amitriptyline/cyclobenzaprine mainly for sleep.
  • Avoid routine NSAIDs, benzodiazepines, and avoid strong opioids (harms outweigh benefits); tramadol only as short-term rescue in select cases.

Care delivery: shared decision-making, explain nociplastic pain model, use PSD/Patient-Reported Outcomes to track progress; de-escalate ineffective drugs.

Complications and Prognosis

Complications

• Functional limitation
• Reduced QoL
• Absenteeism and work disability
• Polypharmacy
• Medication adverse effects
• Increased suicidal ideation/attempts compared with general population

Prognosis

• Fluctuating but modifiable course
• Many improve with non-pharmacological, multicomponent care
• Poorer prognosis with high baseline PSD, severe sleep disturbance, depression/anxiety, catastrophising, obesity, and persistent stressors [2,5].

References

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2. Häuser W, Ablin J, Fitzcharles MA, et al. Fibromyalgia. Nat Rev Dis Primers. 2015;1:15022.
   
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9. Grayston R, Czanner G, Elhadd K, et al. A systematic review and meta-analysis of small fiber pathology in fibromyalgia. Semin Arthritis Rheum. 2019;48(5):933-940.
   
10. Albrecht DS, Forsberg A, Sandström A, et al. Brain glial activation in fibromyalgia — a [11C]-PBR28 PET study. Brain Behav Immun. 2019;75:72-83.
    
11. Clauw DJ, Häuser W, Cohen SP, Fitzcharles MA. Considering the potential of centralised pain in primary care. Mayo Clin Proc. 2019;94(4):736-746.
    
12. Arnold LM, Bennett RM, Crofford LJ, et al. AAPT Diagnostic Criteria for Fibromyalgia. Pain. 2019;160(9):1965-1973.
    
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