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Article
Nature Medicine  2, 1248 - 1250 (1996)
doi:10.1038/nm1196-1248

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

Robert W. Gear1, Christine Miaskowski2, Newton C. Gordon3, Steven M. Paul2, 4, Philip H. Heller5 & Jon D. Levine3, 6, 7

  1Department of Restorative Dentistry, Box 0758; University of California-San Francisco, San Francisco, California 94143-0452, USA

  2Department of Physiological Nursing, Box 0610; University of California-San Francisco, San Francisco, California 94143-0452, USA

  3Department of Oral and Maxillofacial Surgery, Box 0756; University of California-San Francisco, San Francisco, California 94143-0452, USA

  4Department of Epidemiology and Biostatistics, Box 0604; University of California-San Francisco, San Francisco, California 94143-0452, USA

  5Kaiser Foundation Hospital, Hayward, California 94545, USA.

  6Division of Rheumatology, Department of Medicine, S-1334 (Box 0452), University of California-San Francisco, San Francisco, California 94143-0452, USA

  7Correspondence should be addressed to J.D.L. at the address in 6.

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 kappa−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 kappa−opioid agonism. In order to determine whether there are sex differences associated with kappa−opioid agonism, the analgesic efficacy of two other predominantly kappa−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 kappa−opioid analgesia is greater in females than in males, probably reflecting a difference in kappa−opioid−activated endogenous pain modulating circuits.

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