Morphine responses and experimental pain: Sex differences in side effects and cardiovascular responses but not analgesia

Sex differences in analgesic responses to μ opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to μ opioids, the analgesic effects of intravenous morphine (0.08 mg/kg) were determined in healthy women (n = 61) and men (n = 39) by using 3 experimental pain models, heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both morphine and saline, which occurred on separate days in counterbalanced order. Although morphine produced significant analgesic effects for all pain stimuli, no significant sex differences in morphine analgesia emerged. However, morphine attenuated cardiovascular reactivity to the ischemic pain task in men but not women, and women reported significantly more drug-related adverse effects than men. These findings are in contrast with some recent clinical and experimental results suggesting more robust analgesic response to μ opioids among women compared to men, although the data indicate that sex differences in non-analgesic effects of morphine were present. These results suggest that sex differences in responses to morphine might depend on the pain model and/or drug dose as well as the specific end point assessed.