Can Offset Analgesia Magnitude Provide Additional Information About Endogenous Pain Modulation in People With Knee Osteoarthritis? An Experimental Study

Objectives: To investigate the relationship between offset analgesia magnitude and the responsiveness to conditioned pain modulation (CPM), temporal summation of (second) pain (TSP), and clinical pain severity in people with knee osteoarthritis (KOA). Methods: Electrical stimuli were applied to 88 participants with KOA to measure offset analgesia at the volar forearm of the dominant hand, and CPM and TSP at the most symptomatic knee and ipsilateral volar wrist. Clinical pain severity was assessed using the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOSPAIN). Linear mixed-effects models evaluated pain modulatory effects across all tests, and Spearman partial correlations assessed associations between offset analgesia, CPM, TSP, and KOOSPAIN while accounting for covariates of interest. Participants unable to validly finish all psychophysical tests were excluded from effect and correlation analyses but were evaluated for predictors of nonvalid completion using bivariate Stochastic Search Variable Selection. Results: Significant pain modulation was observed across all psychophysical tests (P<0.05), and no meaningful predictors of nonvalid test completion were found. Offset analgesia magnitude did not significantly correlate with CPM, TSP, or KOOSPAIN (P >= 0.05), with a maximum partial correlation coefficient of rho=0.21. Discussion: Offset analgesia was not associated with CPM, TSP, or KOOSPAIN in people with KOA. Despite the lack of case-control studies comparing offset analgesia between people with KOA and healthy controls, these findings suggest that offset analgesia may provide information about endogenous pain modulation beyond CPM and TSP, though its clinical translation remains uncertain.