Nalbuphine,
pentazocine, and
butorphanol, mixed agonist/antagonist
opioids that induce
analgesia by acting predominantly at
kappa opioid receptors, have recently been shown in single-dose studies to have greater
analgesic efficacy in women than in men. In the current experiments, the first placebo controlled dose response study of
opioid analgesic efficacy that examines for gender differences,
nalbuphine (5, 10, or 20 mg) and placebo were evaluated in 62 men and 69 women for the treatment of moderate to severe
postoperative pain following extraction of impacted wisdom teeth. In a randomized, open injection, double blind experimental design,
pain intensity was recorded on
a 10 cm visual analog scale (VAS) immediately prior to
drug administration (baseline) and at 20 min intervals thereafter. Although responses to placebo were similar in men and women, for all doses of
nalbuphine women exhibited significantly greater
analgesic response than men, compatible with our previous results. Unexpectedly, men receiving the 5 mg dose of
nalbuphine experienced significantly greater
pain than those receiving placebo; only the 20 mg dose of
nalbuphine in men produced significant
analgesia compared to placebo. While a similar antianalgesic effect was not observed in women, only the 10 mg dose of
nalbuphine produced significant
analgesia compared to placebo. These results suggest that the optimal
analgesic dose of
nalbuphine for women is lower than the highest dose that can be safely administered. In contrast, the antianalgesic effect of
nalbuphine suggests avoidance of its routine use for postoperative
analgesia in men until further studies clarify this issue. Because gender differences in other mixed kappa agonists/antagonists (i.e.
pentazocine and
butorphanol) have previously been shown, these results may generally apply to this class of
opioid analgesics.