Conditioned pain modulation (CPM) protocols index magnitude of descending pain inhibition. This study evaluated whether degree of CPM, controlling for CPM expectancy confounds, was associated with analgesic and subjective responses to morphine, and whether chronic pain status or sex moderated these effects.
Participants included 92 individuals with chronic low back pain (CLBP) and 99 healthy controls, none using daily opioid analgesics. In a crossover design, participants attended two identical laboratory sessions during which they received either intravenous morphine (0.08▒mg/kg) or saline placebo before undergoing evoked pain assessment. In each session, participants engaged in ischemic forearm and heat pain tasks, and a CPM protocol combining ischemic pain (conditioning stimulus) and heat pain (test stimulus). Placebo-controlled morphine outcomes were derived as differences in pain and subjective effects across drug conditions.
In hierarchical regressions controlling for CPM expectancies, greater placebo condition CPM was associated with less subjective morphine unpleasantness (P=0.001) and greater morphine analgesia (P’s<0.05) on both the ischemic pain task (VAS Pain Intensity and Unpleasantness) and heat pain task (VAS Pain Intensity, McGill Pain Questionnaire-Sensory and Present Pain Intensity [PPI] subscales). There was no moderation by sex or CLBP status, except for the ischemic PPI outcome for which a significant 2-way interaction (P<0.05) was noted, with men showing a stronger positive relationship between CPM and morphine analgesia than women.
Result suggest that CPM might predict analgesic and subjective responses to opioid administration. Further evaluation of CPM as an element of precision pain medicine algorithms may be warranted.

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