Examining Changes in Central and Peripheral Pain As Mediates of Fatigue Improvement: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Objective: Following anti-tumor necrosis factor (anti-TNF) therapy, improvements in rheumatoid arthritis (RA) fatigue are driven by reductions in pain. However, therapies may modify both central and peripheral pain. This study sought to examine the hypothesis that reductions in fatigue after anti-TNF therapy reflect changes in central, not peripheral, pain mechanisms.

Methods: Data came from patients with severe baseline fatigue (Short Form 36 health survey [SF-36] vitality scale ≤12.5; n = 2,652), recruited to the British Society for Rheumatology Biologics Register for RA for commencing anti-TNF therapies between October 2000 and November 2008. Data of interest comprised change over 6 months in fatigue, pain (SF-36 bodily pain scale), and disease activity constituents (Disease Activity Score in 28 joints, erythrocyte sedimentation rate [ESR], global health, swollen joints, and tender joints). Principal components factor analysis with varimax rotation determined latent variables of symptom change; variables were accepted provided they had eigenvalues ≥1.

Results: Six factors were identified, of which 2 met acceptance criteria (eigenvalues of 2.39 and 1.14, respectively). Following rotation, loadings indicated that factor 1 comprised markers of peripheral inflammation: change in ESR, swollen joints, tender joints, and global health. This distinct loading led to factor 1 being labeled peripheral inflammation. Conversely, factor 2 comprised change in pain, fatigue, and global health and an absence of peripheral inflammation markers and was therefore labeled central inflammation.

Conclusion: Following anti-TNF therapies, reductions in fatigue and pain appear to reflect improvements in central, rather than peripheral, inflammation. Therefore, for those seeking to treat fatigue via pain mechanisms, improvements may be maximized by the application of treatment modalities that effectively target central mechanisms.