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Factors underlying differential responsiveness to opioid analgesic medications used in chronic pain management are poorly understood. We tested whether individual differences in endogenous opioid inhibition of chronic low-back pain were associated with the magnitude of acute reductions in back pain ratings after morphine administration.In randomized counterbalanced order over three sessions, 50 chronic low-back pain patients received intravenous naloxone (8 mg), morphine (0.08 mg/kg), or placebo. Back pain intensity was rated predrug and again after peak drug activity was achieved using the McGill Pain Questionnaire-Short Form (Sensory and Affective subscales, VAS Intensity measure). Opioid blockade effect measures to index degree of endogenous opioid inhibition of back pain intensity were derived as the difference between predrug to postdrug changes in pain intensity across placebo and naloxone conditions, with similar morphine responsiveness measures derived across placebo and morphine conditions.Morphine significantly reduced back pain compared with placebo (McGill Pain Questionnaire-Short Form Sensory, VAS; P0.01). There were no overall effects of opioid blockade on back pain intensity. However, individual differences in opioid blockade effects were significantly associated with the degree of acute morphine-related reductions in back pain on all measures, even after controlling for effects of age, sex, and chronic pain duration (P0.03). Individuals exhibiting greater endogenous opioid inhibition of chronic back pain intensity reported less acute relief of back pain with morphine.Morphine appears to provide better acute relief of chronic back pain in individuals with lower natural opioidergic inhibition of chronic pain intensity. Possible implications for personalized medicine are discussed.

Our recent work indicates that endogenous opioid activity influences analgesic responses to opioid medications. This secondary analysis evaluated whether endogenous opioid activity is associated with degree of opioid analgesic adverse effects, and whether chronic pain status and sex affect these adverse effects.Using a double-blind, randomized, placebo-controlled, crossover design, 51 subjects with chronic low back pain and 38 healthy controls participated in 3 separate sessions, undergoing 2 laboratory-evoked pain tasks (ischemic and thermal) after receiving placebo, naloxone, or morphine. Endogenous opioid system function was indexed by the difference in pain responses between the placebo and naloxone conditions. These measures were examined for associations with morphine-related adverse effects.Chronic pain subjects reported significantly greater itching and unpleasant bodily sensations with morphine than controls (P0.05). Across groups, only 6 of 112 possible associations between adverse effects and blockade effects were significant. For the ischemic task, higher endogenous opioid function was associated with greater itching (visual analog scale [VAS]; P0.05), numbness (tolerance; P0.001), dry mouth (tolerance; P0.05), and unpleasant bodily sensations (VAS; P0.05). For the thermal task, higher endogenous opioid function was associated with greater numbness (VAS; P0.05) and feeling carefree (VAS; P0.05). There were no significant main or interaction effects of chronic pain status or sex on these findings.No consistent relationships were observed between endogenous opioid function and morphine-related adverse effects. This is in stark contrast to our previous observation of strong relationships between elevated endogenous opioid function and smaller morphine analgesic effects.