Evidence suggests that gonadal hormones can modulate sensitivity to nociceptive stimuli and opioid antinociception. However, cross-study comparisons addressing the nature of this modulation have been complicated by a number of methodologic factors, including the use of different rodent strains and opioids. The present study examined the influence of estrous cycle and gonadal hormone depletion (ovariectomy) on thermal nociception and opioid antinociception in female F344, Lewis, Long Evans, and Wistar rats. Estrous cycle-dependent differences in nociceptive sensitivity were not observed in any of the strains. Ovariectomy decreased nociceptive sensitivity relative to their intact female counterparts. In normal cycling females, morphine and buprenorphine were generally most potent in metestrus and proestrus and least potent in estrus. The magnitude of these differences was consistently larger with buprenorphine. Ovariectomy increased the antinociceptive potency of morphine and buprenorphine, with this effect also being larger with buprenorphine. These data suggest that in adult females of a number of rat strains, estrous cycle and gonadal hormone depletion modulate the antinociceptive potency of opioids, with the magnitude of this effect being dependent on the type of opioid. In contrast, depletion of gonadal hormones, but not estrous cycle, modulates thermal nociceptive sensitivity in adult female rats.
Perspective: Gonadal hormones influence opioid antinociception, and this effect is apparent across different genetic backgrounds. These results suggest that the phase of the menstrual cycle might alter the effectiveness of certain opioids administered to relieve pain in women.