Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats

Eur J Pharmacol. 2002 Oct 4;452(2):163-73. doi: 10.1016/s0014-2999(02)02274-4.


Previous studies indicate that in antinociceptive procedures employing thermal, chemical and electrical stimuli, opioids are generally more potent in male than female rodents. The purpose of the present study was to examine nociception and opioid antinociception in male and female rats using a mechanical nociceptive stimulus. Results indicated that males had a higher threshold for nociception, and in tests in which a constant pressure was applied to the hindpaw, the paw withdrawal latencies were consistently longer in males. Opioids with activity at the mu receptor, including levorphanol, morphine, dezocine, buprenorphine, butorphanol and nalbuphine, were generally more potent and/or effective in males. In contrast, sex differences were not consistently observed with the kappa-opioid receptor agonists spiradoline, (5,7,8b)-N-methyl-N[2-1(1-pyrrolidinyl),1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U69593), trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide (U50488), enadoline, ethylketocyclazocine, and nalorphine. These findings suggest that males and females differ in their responsiveness to mechanical nociception and that sex differences in sensitivity to kappa-, but not mu-, opioid receptor agonists are specific to certain nociceptive stimulus modalities.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics / pharmacology*
  • Analgesics, Opioid / pharmacology
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Pain Measurement / drug effects*
  • Pain Measurement / methods
  • Physical Stimulation / methods
  • Rats
  • Rats, Inbred F344
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / physiology
  • Receptors, Opioid, mu / agonists*
  • Receptors, Opioid, mu / physiology
  • Sex Characteristics*


  • Analgesics
  • Analgesics, Opioid
  • Receptors, Opioid, kappa
  • Receptors, Opioid, mu