Gender Differences in Pain Management: The Effect of Sexual Dimorphism

HONOLULU, HI—At the American Pain Society's 31st Annual Scientific Meeting, Jon Levine, MD, PhD discussed recent data showing that kappa-opioids, generally observed to be less effective in providing pain relief than mu-receptor opioids, were not only equally effective in producing pain relief in a female patient population, but were also associated with a reduced incidence of adverse effects and greater overall patient satisfaction.

Single-dose studies have shown that kappa-opioid analgesics such as nalbuphine, pentazocine, and butorphanol have greater analgesic efficacy in women than in men. Dr. Levine presented data from one of these studies showing that while low dose nalbuphine 5mg achieved pain relief early on in both men and women, pain relief improved and was maintained over time for women whereas a significant anti-analgesic effect was noted in men, resulting in pain worse than at baseline.

“The concept behind the pathways of pain, however, is far more complex and involves more than one receptor, often with varying effects between genders,” stated Dr. Levine. To evaluate the effects of multiple receptors, a study was conducted in which a low dose of the non-selective opioid receptor antagonist naloxone 0.4mg was added to nalbuphine 5mg to assess if concomitant therapy would eliminate the sex difference and enhance analgesia in both sexes. To further assess the dose-dependent analgesic effects of nalbuphine and the anti-analgesic effects in men, a lower dose of nalbuphine 2.5mg, with and without naloxone, was also evaluated in patients with dental post-operative pain. In women, nalbuphine alone induced modest, short duration analgesia, which was not affected by the addition of naloxone. In men, nalbuphine alone produced analgesia relief early on but resulted in pain enhancement over time. The addition of naloxone did negate the anti-analgesic effect in men, however.

Dr. Levine concluded that kappa-opioid analgesia is greater in females than in males, probably reflecting a difference in kappa-opioid-activated endogenous pain modulating circuits in the central nervous system.