Data Sheet 1_Association between changes in conditioned pain modulation efficiency and pain sensitivity: a randomized controlled trial.pdf

Conditioned pain modulation (CPM) reflects endogenous inhibitory capacity and may demonstrate neuroplastic adaptations with repeated activation. However, the association between CPM efficiency changes and pain sensitivity remains unclear. This planned secondary analysis examined whether improvements in CPM efficiency were associated with changes in quantitative sensory testing (QST) measures and psychological factors in healthy adults. Study design, participants, and primary intervention effects have been reported previously in the primary trial publication. Sixty participants (aged 18–75 years) were randomized to high CPM exposure (five sessions), low CPM exposure (two sessions), or no CPM exposure groups. Multiple linear regression examined associations between changes in CPM efficiency and QST measures (thermal and pressure pain thresholds, tolerance, and ratings) and psychological factors (depression, anxiety, fear of pain, affect, and expectations), controlling for group and age. Improvements in CPM efficiency significantly predicted increases in heat pain threshold temperature (β = −1.90, p < 0.001, R2 = 0.43) and heat tolerance temperature (β = −0.56, p = 0.010, R2 = 0.34), indicating that participants required higher temperatures to detect and tolerate pain. However, pain intensity ratings at these thresholds remained unchanged. Age independently predicted smaller threshold improvements (β = −0.11, p < 0.001). No associations emerged between CPM changes and pressure pain measures, aftersensations, or psychological factors. CPM-induced neuroplasticity selectively enhanced thermal nociceptive detection through descending modulation without altering suprathreshold pain intensity encoding or affecting mechanical pain pathways. CPM induced with thermal stimuli functions as a thermal-specific biomarker rather than a global pain sensitivity indicator, with implications for clinical assessment and interventions targeting descending inhibitory pathways.