Sex differences in morphine analgesia - An experimental study in healthy volunteers

Background Animal and human studies Indicate the existence of important sex -related differences in opioid-mediated behavior, In this study the authors examined the influence of morphine oil experimentally induced pain in heal thy male and female volunteers, Methods: Young healthy men and women (10 of each sex) received intravenous morphine (bolus 0.1.mg/kg dose followed by an infusion of 0.030 mg . kg(-1) . h(-1) for 1 h). Pain threshold and pain tolerance ill response to a grad ual Increase in transcutaneous electrical stimulation, as well as plasma co ncentrations of morphine and its major metabolites (morphine-6-glucuronide and morphine-3-glucuronide) were determined at regular intervals up to 7 h after the start of morphine infusion. A population pharmacodynamic model wa s used to analyze the morphine-induced changes in stimulus intensity. The I mprovement of the model fits by Inclusion of covariates (sex, age, weight, lean body mass) was tested for significance. The model is characterized by baseline current, a rate constant for equilibrium between plasma and effect -site morphine concentrations (k(e0)), and analgesic potency(AC(50) or the morphine concentration causing a 100% increase in stimulus intensity for re sponse), Results: The inclusion of the covariates age, weight, and lean body mass di d not improve the model fits for any of the model parameters. For both pain threshold and tolerance, a significant dependency on sex was observed for the parameters k(e0), (pain threshold: 0.0070 +/- 0.0013 (+/- SE) min(-1) i n men vs. 0.0030 +/- 0.0005 min(-1) in women; pain tolerance: 0.0073 +/- 0. 0012 min(-1) in men l's. 0.0024 +/- 0.0005 min(-1) in women) and AC(50) (pa in threshold: 71.2 +/- 10.5 nm in men vs. 41.7 +/- 8.4 nm in women; pain to lerance: 76.5 +/- 7.4 nar in men vs, 32.9 +/- 7.9 nm in women), Baseline cu rrents cc ere similar for both sexes: 21.4 +/- 1.6 mA for pain threshold an d 39.1 +/- 2.3 mA for pain tolerance. Concentrations of morphine, morphine- 3-glucuroaide, and morphine-6-glucuronide did not differ between men and wo men. Conclusions: These data show sex differences in morphine analgesia, with gr eater morphine potency but slower speed of onset and offset in women, The d ata are in agreement with observations of sex differences in morphine-induc ed respiratory depression and may explain higher postoperative opioid consu mption in men relative to women.