Background/Purpose: Inefficiency of descending conditioned pain modulation (CPM) is present in 42-55% of individuals with knee osteoarthritis (OA), which can contribute to more pain and may result in poor response to current treatments. Depressive symptoms can induce increased activity in the forebrain region and limbic system that may influence the descending conditioned pain modulatory pathways. The extent to which depressive symptoms may be a risk factor for alterations in the descending pathways may be clinically important to identify new therapeutic targets for better pain management in people with knee OA. We therefore sought to examine the relation of depressive symptoms to presence and development of inefficient CPM over two years in people with or at risk of knee OA.

Methods: We used data from the Multicenter Osteoarthritis (MOST) Study, a NIH-funded longitudinal cohort of individuals with or at risk of knee OA. We defined depressive symptoms as a score of ≥16 on the Center for Epidemiologic Studies Depression Scale (CES-D). CPM was assessed with pressure pain threshold (PPT) at the wrist as the test stimulus and forearm ischemia as the conditioning stimulus. We calculated the ratio of post-conditioning stimulus PPT to the pre-conditioning stimulus PPT and defined inefficient CPM as a ratio < 1.12 of the post-conditioning stimulus PPT to pre-conditioning stimulus PPT based upon published data. For the main analysis, we limited our sample to those with efficient CPM at baseline to assess the relation of depressive symptoms to development of inefficient CPM over two years using logistic regression, adjusting for age, sex, and BMI. Because of concerns regarding potential collider bias given that depressive symptoms are often chronic and likely preceded our study baseline, we additionally performed 2 analyses using the whole study sample: 1) a cross-sectional analysis at baseline; 2) a longitudinal analysis evaluating change in CPM ratio over two years using linear regression; this analysis also aimed to account for potential misclassification of categorization of CPM status.

Results: 1033 participants were included in the main analysis (mean age 65±10.5 years, mean BMI 29.5±5.7 kg/m², 41% female). Of those, 13% had depressive symptoms at baseline and 45% developed inefficient CPM over two years. Compared to those without depressive symptoms at baseline, depressive symptoms were associated with 39% reduced odds of developing inefficient CPM (Table). When we included whole sample (N=2761) in the cross-sectional analysis, depressive symptoms were non-significantly associated with 14% reduced odds of being inefficient CPM. Depressive symptoms were not associated with change in CPM over two years.

Conclusion: In contrast to our hypothesis, we found that having depressive symptoms was protective of development of inefficient CPM in knee OA. These findings suggest that depressive symptoms may potentially contribute to strengthening or activation of the descending conditioned pain modulatory pathways, such as through enhanced central inhibitory neurotransmitter levels or other central mechanisms.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relation-of-depressive-symptoms-to-alterations-in-conditioned-pain-modulation-in-knee-osteoarthritis-the-multicenter-osteoarthritis-study-most/