Central pain sensitivity is associated with changes in fatigue in RA: data from the CAP-RA study

OBJECTIVES: This observational study examined whether central pain sensitivity is associated with fatigue in RA and whether such associations are explained by pain severity or inflammation. METHODS: Participants with RA provided self-report fatigue (Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire-BRAF-MDQ), pain severity (summated numerical rating scales) and self-reported pain sensitivity (central aspects of pain-CAP) data at baseline (n = 194) and 3 months (n = 114) while under usual care. CAP was modified (M-CAP) by removing the fatigue-associated item. Pain sensitivity was also assessed by 'static' (pressure pain detection threshold) and 'dynamic' (temporal summation, conditioned pain modulation) quantitative sensory testing (QST). Inflammation was assessed using 28-joint disease activity score (DAS28) tender/swollen joint counts, CRP and US imaging (greyscale, power Doppler). Associations between fatigue and central pain sensitivity were explored with multivariable linear-regression modelling. RESULTS: Baseline M-CAP and pain severity were each associated with higher fatigue at baseline (M-CAP: rho = 0.77, P ≤ 0.001; pain: rho = 0.53, P ≤ 0.001) and at 3 months follow-up (M-CAP: rho = 0.72, P ≤ 0.001; pain: rho = 0.47, P ≤ 0.001). M-CAP and pain remained significantly associated with baseline fatigue when included in a single regression model (M-CAP: β = 0.65, P < 0.001; pain: β = 0.21, P < 0.001; R2 = 0.62, P < 0.001). In longitudinal regression models, a decrease in M-CAP was significantly associated with a reduction in fatigue. QST indices and markers of inflammation were not consistently associated with fatigue. CONCLUSION: Self-reported central pain sensitivity (M-CAP) is a strong driver of fatigue over and above inflammation and pain intensity. Treatments targeting central pain mechanisms may be effective at also reducing fatigue in individuals with RA.