| There is increasing evidence that the sex of the organism is a critical factor influencing responses to nociceptive stimuli and opioid antinociceptive agents. Nociceptive pathways and opioids differ along numerous dimensions, and the following studies examine how these factors influence sensitivity to nociceptive stimuli and opioid antinociception in male and female rats.; Experiment 1 examined sex differences in the antinociceptive effects of κ opioids in three rat strains. Males were generally more sensitive than females to κ opioids, with the magnitude of the differences depending on the particular strain tested and the relative efficacy of the opioid. Similar to data obtained with μ opioids, there is also a sexual dimorphism in responsiveness to κ opioids.; Experiment 2 used a mechanical nociceptive stimulus to examine the influence of sex on nociception and opioid antinociception. Similar to assays of thermal nociception, males were less sensitive to mechanical nociceptive stimuli and also more sensitive to the antinociceptive effects of μ opioids. However, in contrast to thermal nociceptive assays, there were no consistent sex differences in κ opioid antinociception. Thus, Experiment 2 identified important conditions that determine differential sensitivity to opioids in males and females.; Experiment 3 examined sex differences to μ opioids in a capsaicin-induced hyperalgesia assay, a model that more closely resembles human clinical pain. Males were again less sensitive to nociceptive stimuli in this assay, as evidenced by decreased hyperalgesic responses to capsaicin. However, in tests examining the ability of opioids to reverse hyperalgesia, there were either no consistent sex differences or females were more sensitive than males. These data contrast with data from assays of short-lasting pain, and indicate that the duration of pain is a critical determinant of the profile of sex differences in antinociception.; In summary, these experiments emphasize the importance of sex in determining sensitivity to nociceptive stimuli and opioid antinociceptive agents across a broad range of procedural parameters. Whereas males were uniformly less sensitive to nociceptive stimuli, the profile of sex differences in antinociception depended on the rat strain, relative efficacy of the opioid, type of nociceptive stimulus employed, and duration of the nociceptive stimulus. |
