In Knee Osteoarthritis, Greater Pain Intensity and Disability Is Associated with Reduced Offset Analgesia

Preclinical work demonstrates that deficits in central pain inhibition contribute to knee osteoarthritis pain. In patients, this remains unclear given mixed findings from studies measuring conditioned pain modulation (CPM), which reflects spatial aspects of central pain inhibition. Time-dependent aspects, measured by offset analgesia, have not been examined. In this study, we sought to determine whether knee osteoarthritis pain was associated with altered offset analgesia. Using a case-control design, participants with moderate-to-severe knee osteoarthritis pain (n=37), mild pain (n=36), and pain-free controls (n=30), matched for age, gender, and body mass index, underwent pain assessment, quantitative sensory testing, and standardized weight-bearing tasks. Offset analgesia at the nonpainful forearm was significantly reduced in knee osteoarthritis (control: -81.7% SD 21.0%, mild: -68.5% SD 23.2%, mod-sev: -64.1% SD 27.5%, 1-way ANOVA F(2,99) = 4.57, p=0.013), with similar results controlling for age, gender, and radiographic knee joint degeneration using linear regression. Offset analgesia measured at the knee was also reduced in knee osteoarthritis groups. In patients, less forearm offset analgesia was associated with greater pain and worse objective performance on 6-minute walk and stair climb tasks. CPM was not different across groups nor associated with mobility-evoked pain or dysfunction. Taken together, these results demonstrate that deficits in offset analgesia are observed in patients with greater pain and functional impairment from knee osteoarthritis, suggesting that dysregulated time-dependent pain inhibition contributes to clinically relevant outcomes in knee osteoarthritis. This study was registered on clinicaltrials.gov (NCT05003323) and funded by the University of Pittsburgh and the NIH (NINDS K23NS123429).