Overview

Chronic widespread pain (CWP) is a nociplastic pain phenotype defined by persistent (≥3 months) pain affecting multiple body regions, with high comorbidity with fatigue, sleep disturbance, mood symptoms and functional impairment. The pooled global prevalence is ~10% (women>men), with higher rates in lower-HDI settings. CWP is recognised in ICD-11 within the chronic primary pain family (fibromyalgia is included).

Major complications include work disability, reduced quality of life and increased all-cause mortality—largely mediated by adverse lifestyle factors—highlighting the need for person-centred, non-drug first care.

Anatomy & Physiology 

• Ascending pathways: peripheral A-delta/C fibres → dorsal horn → spinothalamic/limbic projections → thalamus → S1/S2, insula, anterior cingulate.
  
• Descending modulation: PAG–RVM circuits modulate dorsal horn via monoamines (5-HT/NA) and endogenous opioids.
  
• Sleep–pain crosstalk: slow-wave sleep supports descending inhibition; deprivation augments temporal summation.
  

Autonomic–HPA axis: sympathetic arousal and cortisol rhythms influence pain thresholds and fatigue.

Aetiology and Risk Factors

Aetiology (multifactorial)

• Central sensitisation with impaired descending inhibition (nociplastic mechanism).
  
• Neuroimmune/glial activation within pain networks (insular/ACC circuits).
  
• Multisite pain loading and prior regional pains predispose to generalisation.
  
• Biopsychosocial drivers: adverse life events, psychological distress, deconditioning. (WHO)
  

Risk factors

Female sex, midlife; sleep problems (initiation/maintenance/early awakening/non-restorative sleep) and fatigue (independent predictors over 5–18 years); higher baseline number of pain sites; low socioeconomic/HDI; obesity/inactivity; anxiety/depression; manual work. (BioMed Central)

Pathophysiology (chronological flow)

• Predisposition (sex, genetics, early adversity, low SES) → lower thresholds for central pain amplification.
  
• Triggers (regional pain, injury/stress, sleep disruption) → increased peripheral input and stress reactivity.
  
• CNS changes: augmented temporal summation, reduced conditioned pain modulation, altered insula/ACC connectivity and neurotransmitters (↓NA/5-HT, ↑glutamate); glial activation sustains hyperexcitability.
  

Systemic correlates: autonomic dysregulation and sleep fragmentation perpetuate pain and fatigue → generalisation from regional to widespread pain.

Clinical Manifestations

• Pain: chronic (≥3 months), widespread or multisite; migratory/variable intensity; hyperalgesia/allodynia to light pressure.
  
• Somatic symptoms: fatigue, morning stiffness, headaches/migraine, paresthesias, irritable bowel/bladder, TMJ pain.
  
• Sleep/cognitive: non-restorative sleep, insomnia, “brain-fog” (attention/processing speed).
  
• Mood/autonomic: anxiety/depression common; orthostatic intolerance, palpitations, thermodysregulation.
  
• Examination: normal joint and neurological exam; diffuse tenderness to ~4 kg pressure; no synovitis or objective weakness.
  

Diagnosis

• Case definition (preferred, post-2010): WP2019—pain in ≥4/5 regions and ≥7/15 pain sites, duration ≥3 months; developed to replace ambiguous 1990 “above/below waist, both sides, axial” definition and to integrate with 2016 FM mapping. (De Gruyter Brill)
  
• ICD-11 context: classify as chronic primary pain (MG30.01 chronic widespread pain) unless a specific disease fully explains severity/impact (then “secondary”). (WHO)
  
• Investigations (rule-out/minimise over-testing): FBC, ESR/CRP, TSH, CMP ± CK; screen for OSA when indicated; B12/ferritin if fatigue; autoimmune serology only if clinical suspicion (e.g., synovitis/rashes). NICE encourages person-centred assessment and avoids indiscriminate testing. (NICE)
  
• Key differentials and discriminators:
  
  • Fibromyalgia (meets ACR 2016 FM criteria with higher symptom burden, but phenotypes overlap).
    
  • Inflammatory rheumatic disease (objective synovitis, raised CRP/ESR, erosions).
    
  • Hypothyroidism (TSH↑, clinical features).
    
  • Myopathies (objective weakness, CK↑).
    
  • Small fibre neuropathy (length-dependent burning, reduced IENFD).
    
  • Polymyalgia rheumatica (older age, shoulder/hip girdle stiffness, CRP/ESR↑).

Table 1. Diagnostic frameworks at a glance

Classification (disease categories)

• By ICD-11: Chronic primary widespread pain (MG30.01) vs chronic secondary widespread pain (e.g., multiple regional pain conditions or systemic disease fully explaining pain). (WHO)
  
• By mechanism: nociplastic-predominant (core) with variable nociceptive/neuropathic contributions.
  
• By severity: symptom burden (e.g., polysymptomatic distress/WPI bands).
  Acronym (features): SPREAD = Sleep disturbance, Psychological distress, Regions ≥4, Exclude fully explanatory disease, Activity graded, Duration ≥3 months.
  

Treatment

• Core for all: education on nociplastic pain, supervised exercise/physical activity (graded aerobic/strength/aquatic), and psychological therapies (CBT/ACT) with shared decision-making; consider acupuncture (time-limited) per NICE. (NICE)
  
• Medications (for chronic primary pain): consider antidepressants (e.g., amitriptyline, duloxetine, fluoxetine, paroxetine, sertraline, citalopram) after shared decision-making; review regularly for benefit–harm. Do not initiate opioids, benzodiazepines, antiepileptics (except as part of specialist care), NSAIDs or corticosteroids for chronic primary pain. (NICE)
  
• Address comorbidities: optimise sleep (OSA assessment, sleep hygiene), treat mood disorders, weight management, pacing/goal-setting; support return-to-function plans. (NICE)

Table 2. Management quick guide

Complications and Prognosis

Complications

• Functional limitation, reduced QoL and work participation; high healthcare use/polypharmacy; excess mortality relative to non-CWP peers—attenuated by addressing lifestyle risks (physical inactivity, smoking, diet, obesity). (ard.bmj.com)
  Prognosis
  

Fluctuating but modifiable course; many improve with multicomponent care; poorer prognosis with high symptom burden, severe sleep disturbance, persistent psychosocial stressors and multiple pain sites. (BioMed Central)

References

1. Wolfe F, Butler SH, Fitzcharles MA, et al. Revised chronic widespread pain criteria: development from and integration with fibromyalgia criteria. Scand J Pain. 2020;20(1):77-86. (De Gruyter Brill)
2. Treede R-D, Rief W, Barke A, et al. Chronic pain as a symptom or a disease: the IASP classification of chronic pain for ICD-11. Pain. 2019;160(1):19-27. (The Erythromelalgia Association)
3. NICE Guideline NG193. Chronic pain (primary and secondary) in over 16s: assessment of all chronic pain and management of chronic primary pain. 2021. (NICE)
4. Andrews P, Steultjens M, Riskowski J. Chronic widespread pain prevalence in the general population: a systematic review. Eur J Pain. 2018;22(1):5-18. (Wiley Online Library)
5. Aili K, Andersson M, Bremander A, et al. Sleep problems and fatigue as predictors for the onset of chronic widespread pain over a 5- and 18-year perspective. BMC Musculoskelet Disord. 2018;19:390. (BioMed Central)
6. Macfarlane GJ, Barnish MS, Jones GT. Persons with chronic widespread pain experience excess mortality: longitudinal results from UK Biobank and meta-analysis. Ann Rheum Dis. 2017;76(11):1815-1822. (ard.bmj.com, aura.abdn.ac.uk)
7. Butler S, Landmark T, Glette M, Borchgrevink P, Woodhouse A. Chronic widespread pain – the need for a standard definition. Pain. 2016;157(3):541-543. (De Gruyter Brill)