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

J Pain. 2005 Feb;6(2):116-24. doi: 10.1016/j.jpain.2004.11.005.


Sex differences in analgesic responses to mu opioid agonists have been reported, although the direction of these differences varies across studies. To further characterize sex differences in responses to mu 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 mu 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.

Perspective: This study examines morphine responses in women and men by using laboratory pain measures. The results indicate no sex differences in analgesia, but women reported greater side effects, and morphine attenuated cardiovascular responses more strongly among men than women. These results add to the literature regarding sex differences in response to opioids.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Blood Pressure / drug effects
  • Female
  • Heart Rate / drug effects
  • Hot Temperature
  • Humans
  • Ischemia / complications
  • Male
  • Morphine / administration & dosage
  • Morphine / adverse effects*
  • Pain / drug therapy*
  • Pain Threshold / drug effects*
  • Pressure
  • Sex Characteristics*


  • Analgesics, Opioid
  • Morphine