Sex differences in analgesia: a randomized trial of mu versus kappa opioid agonists

South Med J. 2004 Jan;97(1):35-41. doi: 10.1097/01.smj.0000085743.68121.a9.


Objectives: We sought to evaluate whether there is a sex difference in the analgesic response to mu versus kappa opioids in the management of acute moderate to severe pain of injury in the emergency department.

Methods: The study was a randomized, double-blind, clinical trial comparing the prototypical mu-receptor agonist, morphine sulfate, to the prototypical kappa agonist, butorphanol. The primary endpoints were degree of relief by visual analog scores at 30 and 60 minutes. Statistical analysis was performed using Mann-Whitney Utest for nonparametric analysis and repeated-measures analysis of variance.

Results: Ninety-four patients were entered in the study, with 49 (52%) males and 45 (48%) females. Forty-six received morphine sulfate and 48 received butorphanol. There was no difference in demographics in the two groups. At 60 minutes, females had significantly lower visual analog scores with butorphanol compared with morphine (P = 0.046). At 60 minutes, there was a trend for a difference in response of males versus females to morphine, with males responding better than females (P = 0.06).

Conclusion: Females had better pain scores with butorphanol than morphine at 60 minutes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analgesics, Opioid / therapeutic use*
  • Analysis of Variance
  • Butorphanol / therapeutic use*
  • Diastole / drug effects
  • Double-Blind Method
  • Emergency Service, Hospital
  • Female
  • Humans
  • Male
  • Morphine / therapeutic use*
  • Narcotic Antagonists / therapeutic use*
  • Pain / drug therapy*
  • Pain / etiology
  • Pain Measurement
  • Sex Characteristics*
  • Time Factors
  • Treatment Outcome
  • Wounds and Injuries / complications


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Morphine
  • Butorphanol