Characterization of the antinociceptive effect of oxycodone in male and female rats

A number of investigators have shown that sex plays an important role in the analgesic effects of opioids. Typically, the antinociceptive responsiveness to mu opioid agonists such as morphine is greater in male than in female rats. The effect of sex on kappa opioid analgesia is less known. The present study was conducted to examine sex-related differences in responsiveness to oxycodone (putative kappa/mu opioid agonist). This information is important since oxycodone is widely used clinically for treatment of pain. The present results indicated that oxycodone had a greater antinociceptive response in female rats compared to male rats. This sex specific responsiveness to oxycodone, however, was lost with chronic administration. The greater antinociception in female rats was even more prominent with U50,488H (selective kappa agonist). Further, low (subanalgesic) doses of oxycodone and U50,488H enhanced the sensitivity to pain (hyperalgesia) to a greater extent in male than in female rats. This is in contrast to the previously shown greater hyperalgesic effect of subanalgesic doses of the mu opioid agonist, morphine, in female than in male rats. The present findings suggest that sexual dimorphism in the effect of opioids is related to the opioid receptors on which they predominately act.