Centrally mediated pain features predict persistent pain in early inflammatory arthritis: a 2-year prospective study

Patients with inflammatory arthritis (IA) often report pain not necessarily coupled to active inflammation. We previously demonstrated that a significant subset of patients with newly diagnosed IA report features of centrally mediated pain. In this prospective study following the same IA cohort, we tracked the relative contributions of inflammatory/noninflammatory mechanisms to pain over 2 years. We used patient-reported outcome measures (PROMs), clinical data (including ultrasound), and standardised quantitative sensory testing. Mixed-effects regression models examined longitudinal associations. We recruited 66 patients. At 6, 12, and 24 months, 62%, 57%, and 49% of individuals, respectively, reported persistent pain (numerical rating scale ≥3). Using factor-derived composite scores, baseline and longitudinal inflammation was not associated with subsequent pain (b -0.05, P = 0.87), whereas higher centrally mediated pain markers predicted less pain reduction (b 1.41, 95%, P < 0.001). Baseline PROMs of centrally mediated pain (fibromyalgia severity average marginal effect [AME]: 0.94, P < 0.001, painDETECT AME: 1.03, P < 0.001) and mental health (eg, Generalised Anxiety Disorder-7 AME: 1.08, P < 0.001) were the strongest predictors of persistent pain. Baseline trapezius pressure pain threshold (PPT) and conditioned pain modulation (CPM) pain detection threshold (PDT) effect showed modest association (trapezius PPT AME: -0.51, P = 0.054, CPM PDT effect AME: -0.49, P = 0.051) whereas temporal summation of pain (AME: 0.09, P = 0.756) and CPM pain tolerance threshold effect (AME: -0.01, P = 0.964) did not. In our cohort, persistent pain was associated with higher baseline and longitudinal scores for centrally mediated pain according to PROMs rather than inflammation according to joint ultrasound. In IA, early identification and treatment of features of centrally mediated pain may improve pain-related outcomes.