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

Objectives This observational study examined whether central pain sensitivity is associated with fatigue in rheumatoid arthritis (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, c-reactive protein, and ultrasound 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.