Experimental pain models reveal no sex differences in pentazocine analgesia in humans

Background: Accumulating evidence suggests that there are sex differences in analgesic responses to opioid agonists. Several studies using an oral surgery pain model have reported more robust analgesia to kappa-agonist-antagonists (e.g., pentazocine, nalbuphine, butorphanol) among women than among men. However, evidence of sex differences in kappa-agonist-antagonist effects from studies of experimentally induced pain in humans is lacking. Methods: Therefore, the analgesic effects of intravenous pentazocine (0.5 mg/kg) were determined in healthy women (n = 41) and men (n = 38) using three experimental pain models: heat pain, pressure pain, and ischemic pain. Each pain procedure was conducted before and after double-blind administration of both pentazocine and saline, which occurred on separate days in counterbalanced order. Results: Compared with saline, pentazocine produced significant analgesic responses for all pain stimuli. However, no sex differences in pentazocine analgesia emerged. Effect sizes for the sex differences were computed; the magnitude of effects was small, and an equal number of measures showed greater analgesia in men than in women. Also, analgesic responses were not highly correlated across pain modalities, suggesting that different mechanisms may underlie analgesia for disparate types of pain. Conclusions: These findings indicate significant analgesic responses to pentazocine in both men and women across multiple experimental pain assays, and the absence of sex differences contrasts with previous data from the oral surgery model. The most likely explanation for the discrepancy in results is that of differences in the pain assays. These findings are important because they suggest that sex differences in opioid analgesia may be specific to certain types of pain.