Individual differences in endogenous opioid function predict analgesic responses to morphine

Factors contributing to differential responses to opioid analgesic medications across individuals are not well understood. This study tested whether individual differences in endogenous opioid systems contribute to variability in responses to a prototypic exogenous opioid analgesic. Participants included 18 healthy individuals and 26 individuals with chronic low back pain (LBP), all using no opioid analgesics. Participants attended 3 identical sessions during which they received either intravenous naloxone (8mg), morphine sulfate (0.08mg/kg), or saline placebo, and then underwent an ischemic forearm pain task followed by a computerized heat pain task (Medoc TSA-II). Within-subject differences between acute pain responses in the placebo condition versus the naloxone and morphine conditions were derived as indices of endogenous opioid function and exogenous opioid analgesic responses, respectively. Correlation analyses indicated significant inverse associations between endogenous opioid function and exogenous opioid responses for ischemic threshold (r = -0.46, p<.01) and tolerance (r = -0.63, p<.001), intra-task numeric intensity ratings (NRS; r = -0.70, p<.001), and post-task McGill Pain Questionnaire (MPQ) Sensory (r = -0.43, p<.01) and Total (r = -0.41, p<.01) scores. All thermal pain task outcomes revealed significant inverse associations between endogenous opioid function and exogenous opioid responses, including heat pain threshold (r = -0.43, p<.01) and tolerance (r = -0.60, p<.001); MPQ Sensory (r = -0.65, p<.001), Affective (r = -0.63, p<.001), and Total (r = -0.64, p<.001) scores, and visual analog pain intensity (r = -0.50, p<.001) and unpleasantness (r = -0.45, p<.01) measures. Ten of these 12 correlations remained significant after controlling for differences in placebo pain level (partial correlations). Multivariate analyses indicated that independent of LBP status, endogenous opioid function indices for both ischemic and thermal tasks predicted the set of morphine responses for the respective pain task. Results highlight that individual differences in endogenous opioid function account for substantial inter-individual variability in morphine analgesic responses. Findings may have implications for personalized pain medicine.