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Kappa–opioids produce significantly greater analgesia in women than in men


Sex differences in human responses to nociceptive stimuli and painful pathological conditions have generally indicated that women report higher pain levels or exhibit less tolerance than men for given stimulus intensities (reviewed in ref. 1 and 2). However, studies have not evaluated sex differences in analgesic responses. We recently reported that the opioid agonist–antagonist pentazocine, which acts predominantly at κ–receptors, produced significantly better postoperative analgesia in females than in males3,4 in patients who underwent surgery for the removal of their third molars (wisdom teeth). In the current study, we evaluated the hypothesis that this sex difference is a characteristic of κ–opioid agonism. In order to determine whether there are sex differences associated with κ–opioid agonism, the analgesic efficacy of two other predominantly κ–opioid analgesics, nalbuphine and butorphanol, was compared in males and females who underwent surgery for the removal of third molar teeth. We found that both nalbuphine and butorphanol produced significantly greater analgesia in females as compared with males. Considering our earlier findings, we conclude that κ–opioid analgesia is greater in females than in males, probably reflecting a difference in κ–opioid–activated endogenous pain modulating circuits.

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Gear, R., Miaskowski, C., Gordon, N. et al. Kappa–opioids produce significantly greater analgesia in women than in men. Nat Med 2, 1248–1250 (1996).

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