Sex differences in μ-opioid receptor expression in trigeminal ganglia under a myositis condition in rats

X Zhang1, Y Zhang, J Asgar

  • 1Department of Anesthesiology, Hospital of Stomatology, The First Affiliated Hospital, China Medical University, Shenyang, China.

Abstract

Insights

Testosterone regulates μ-opioid receptor (MOR) expression in trigeminal ganglia during inflammation, influencing pain relief from peripheral opioids. Sex differences in anti-hyperalgesia are linked to these peripheral opioid receptor levels.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Peripheral opioid receptor expression increases with inflammation, enhancing opioid efficacy.
  • Sex differences in inflammatory effects on trigeminal ganglia μ-opioid receptor (MOR) expression are not well understood.

Purpose of the Study:

  • To investigate sex differences in MOR expression in trigeminal ganglia (TG) under inflammatory conditions.
  • To determine the role of cytokines and gonadal hormones in regulating MOR expression.
  • To assess the impact of these factors on the efficacy of peripherally administered opioids.

Main Methods:

  • Assessed MOR mRNA and protein in rat TG following Complete Freund's Adjuvant (CFA)-induced muscle inflammation.
  • Examined cytokine-induced MOR mRNA changes in TG cultures from intact and gonadectomized rats, with and without testosterone replacement.
  • Conducted behavioral studies on MOR agonist efficacy in male and female rats with myositis.

Main Results:

  • CFA and cytokine treatments upregulated MOR in male rat TG, but not female.
  • Testosterone replacement restored cytokine-induced MOR mRNA upregulation in orchidectomized male rats.
  • The MOR agonist DAMGO attenuated inflammation-induced hypersensitivity only in intact male rats.

Conclusions:

  • Testosterone is crucial for regulating TG MOR expression during inflammation.
  • Sex differences in the anti-hyperalgesic effects of peripheral opioids are partly mediated by peripheral MOR levels.