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Sex differences in opioid antinociception

R E Bartok1, R M Craft

  • 1Department of Psychology, Washington State University, Pullman 99164-4820, USA.

The Journal of Pharmacology and Experimental Therapeutics
|August 1, 1997
PubMed
Summary
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Opioid pain relief varies by sex, dose, and time. This study found sex differences in kappa and delta opioid effects, contrasting with previous research, possibly due to comprehensive testing methods.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Pain Research

Background:

  • Previous research suggests male rodents exhibit greater antinociception from mu-opioid agonists compared to females.
  • Understanding sex-based differences in opioid efficacy is crucial for pain management.
  • Variations in study design, including dose, time, and testing methods, may explain conflicting findings.

Purpose of the Study:

  • To investigate sex differences in antinociception across various opioid receptor subtypes (mu, kappa, delta).
  • To examine the influence of dose, time, and assay type on opioid-induced antinociception in male and female rats.
  • To compare findings with previous studies and explore reasons for discrepancies.

Main Methods:

  • Adult male and female Sprague-Dawley rats were used.

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  • Time-effect curves were generated for mu (fentanyl, buprenorphine), kappa (U69,593, bremazocine), and delta (DPDPE, deltorphin) agonists.
  • Antinociception was assessed using the hot-plate and tail-withdrawal assays at multiple doses and time points.

    • Main Results:

    • Sex differences in antinociception were observed for kappa and delta agonists, dependent on assay, dose, and time.
    • Peak effects for some kappa and delta agonists occurred earlier in females.
    • Higher doses of delta opioids produced greater antinociception in males on the hot-plate assay, while females showed greater tail-withdrawal antinociception with bremazocine.

    Conclusions:

    • Sex differences in opioid antinociception are complex and depend on the specific opioid, dose, time, and testing method.
    • The comprehensive dose- and time-course analysis revealed nuanced sex differences not apparent in studies using single time points.
    • Discrepancies with prior research may stem from methodological differences, including acute versus repeated testing and opioid tolerance development.