Related Experiment Video
Updated: May 10, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Sex differences in μ-opioid receptor expression in trigeminal ganglia under a myositis condition in rats
1Department of Anesthesiology, Hospital of Stomatology, The First Affiliated Hospital, China Medical University, Shenyang, China.
Background:
Peripheral opioid receptor expression is up-regulated under inflammatory conditions, which leads to the increased efficacy of peripherally administered opioids. Sex differences in the effects of inflammation, cytokines and gonadal hormones on μ-opioid receptor (MOR) expression in trigeminal ganglia (TG) are not well understood.
Methods:
MOR mRNA and protein levels in TG from male and female Sprague Dawley rats following complete Freund's adjuvant (CFA)-induced muscle inflammation were assessed. Cytokine-induced changes in MOR mRNA expression from TG cultures prepared from intact and gonadectomized male and female, and gonadectomized male rats with testosterone replacement were examined. Behavioural experiments were then performed to examine the efficacy of a peripherally administered MOR agonist in male, female and gonadectomized male rats under a myositis condition.
Results:
CFA and cytokine treatments induced significant up-regulation of MOR expression in TG from male, but not from female, rats. The cytokine-induced up-regulation of MOR mRNA expression was prevented in TG from orchidectomized (GDX) male rats, which was restored with testosterone replacement. Peripherally administered DAMGO, a specific MOR agonist, significantly attenuated CFA-induced masseter mechanical hypersensitivity only in intact male rats.
Conclusions:
Collectively, these data indicate that testosterone plays a key role in the regulation of MOR in TG under inflammatory conditions, and that sex differences in the anti-hyperalgesic effects of peripherally administered opioids are, in part, mediated by peripheral opioid receptor expression levels.
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.
Related Concept Videos
Opioid Receptors: Overview
Analgesia and Pain Management

