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

Abstract

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 males 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.

Gender and pain upon movement are associated with the requirements for postoperative patient-controllediv analgesia: a prospective survey of 2,298 Chinese patients

“…Gear et al have reported that postdental surgery pain relief by opioids acting at the -receptor was greater amongst females than amongst males. 6 Miaskowsi and Levine recently reviewed studies for the period from 1966 to 1998 in which a PCA was used to administer opioids for postoperative pain, and found that a slight majority of studies noted larger PCA opioid consumption amongst males as compared to females 1,[7][8][9] in line with our results. The reasons for this gender related difference remain unclear and several mechanisms may be invoked.…”

The melanocortin-1 receptor gene mediates female-specific mechanisms of analgesia in mice and humans

“…42). Gear and colleagues (10)(11)(12)(13), in contrast, have reported that women are more sensitive to the inhibition of molar extraction pain by a number of nonselective -opioid analgesics including pentazocine. We observed a trend in the opposite direction presently: toward greater analgesia in nonredheaded men than women.…”

Nociception in cyclooxygenase isozyme-deficient mice

“…Gender differences may exist in pain-processing pathways. Recent studies have demonstrated that female patients experience pain relief with agonist opiate analgesics such as pentazocine, whereas male patients do not (27). opiate receptors together with COX-2 mRNA have been identified in the dorsal horn of the spinal cord, and these mechanisms may interact differently in male and female animals (28).…”