Greater Conditioned Pain Modulation Is Associated With Enhanced Morphine Analgesia in Healthy Individuals and Patients With Chronic Low Back Pain

Objectives: Conditioned pain modulation (CPM) protocols index magnitude of descending pain inhibition. This study evaluated whether the 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. Materials and Methods: Participants included 92 individuals with chronic low back pain and 99 healthy controls, none using daily opioid analgesics. In a cross-over design, participants attended 2 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. Results: 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 (Visual Analog Scale Pain Intensity and Unpleasantness) and heat pain task (Visual Analog Scale Pain Intensity, McGill Pain Questionnaire-Sensory, and Present Pain Intensity subscales). There was no moderation by sex or chronic low back pain status, except for the ischemic Present Pain Intensity 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. Discussion: Results 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.