Conditioned Pain Modulation and Pleasant Pain Relief as Complementary Processes Reflecting Individual Differences in Pain Coping: A Clustering Approach

BACKGROUND: Pain perception is the result of different modulatory mechanisms. Inhibition, via descending brainstem mechanisms, is key to pain reduction and is typically elicited by the cold pressor test (CPT). Recently, a compensatory hedonic response has been observed after CPT interruption, thought to facilitate return to homeostasis. Although both are triggered by the CPT, how these mechanisms vary across individuals remains unknown. METHODS: Pain-free individuals (n = 200) participated in a quantitative sensory testing protocol assessing inhibition (via conditioned pain modulation (CPM)) and hedonic (via pleasant pain relief (PPR)) responses. CPM paradigm involved a tonic heat stimulation, administered before and after a CPT at 10°C. CPM magnitude was calculated as the change in pain ratings following the conditioning stimulus. PPR magnitude was quantified using participants' subjective perception of pain relief immediately following cessation of the CPT. A k-means clustering analysis based on four principal variables was performed to identify distinct response sub-groups. RESULTS: Four clusters provided an optimal solution and explained 58% of the total variance. Cluster 1 demonstrated high CPM and moderate PPR response. In contrast, Cluster 2 demonstrated weak CPM and strong PPR. Cluster 3 appears to be similar to Cluster 2. Finally, Cluster 4 was characterized by both weak CPM and weak PPR associated with low pain perception during the CPT. CONCLUSION: This study supports that two distinct phenomena pre-exist, one leading to inhibition and the other to compensation. Although distinct, there appear to be complementary, with the PPR being stronger in individuals with weaker CPM responses. SIGNIFICANCE STATEMENT: This study highlights the recruitment of a potential hedonic compensatory mechanism when inhibitory resources are insufficient to cope with pain.