ArticleNeuroscience2016
Androgen receptor transcriptionally regulates μ-opioid receptor expression in rat trigeminal ganglia.
Article in Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Effects of intramuscular morphine in men and women with temporomandibular disorder with myofascial pain.Oral diseases · 2018Trial
- Validation of TRPA1 and TRPV1 Antibodies for Expression Detection in Mammalian Cells and Tissues.Journal of neurochemistry · 2026Article
- Effect of Testosterone on Maintenance of Morphine-induced Conditioned Place Preference: Androgen and μ-opioid Receptor Gene Expressions in PFC and NAc of Rats.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Epigenome-wide association study of placental co-methylated regions in newborns for prenatal opioid exposure.Environmental epigenetics · 2025Article
- Article
- The role of gonadal hormones in regulating opioid antinociception.Annals of medicine · 2024Review
- The influence of sex on neuroimmune communication, pain, and physiology.Biology of sex differences · 2024Review
- Modulatory Processes in Craniofacial Pain States.Advances in neurobiology · 2024Article
- HPA axis dysfunction during morphine withdrawal in offspring of female rats exposed to opioids preconception.Neuroscience letters · 2022Article
- Sex differences in opioid receptor mediated effects: Role of androgens.Neuroscience and biobehavioral reviews · 2022Review
- Peripherally Acting Opioids in Orofacial Pain.Frontiers in neuroscience · 2021Review
- Article
- Sex differences in neuro(auto)immunity and chronic sciatic nerve pain.Biology of sex differences · 2020Review
- Testosterone modulation of ethanol effects on the µ-opioid receptor kinetics in castrated rats.Biomedical reports · 2019Article
- Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain.Journal of translational medicine · 2019Article
- Gender aspects of CGRP in migraine.Cephalalgia : an international journal of headache · 2019Review
- Testosterone deficiency in non-cancer opioid-treated patients.Journal of endocrinological investigation · 2018Review
- Diffuse noxious inhibitory controls and brain networks are modulated in a testosterone-dependent manner in Sprague Dawley rats.Behavioural brain research · 2018Article
- Opposing Roles of Estradiol and Testosterone on Stress-Induced Visceral Hypersensitivity in Rats.The journal of pain · 2018Article
- Neonatal Handling Produces Sex Hormone-Dependent Resilience to Stress-Induced Muscle Hyperalgesia in Rats.The journal of pain · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The involvement of testosterone in pain, inflammation, and analgesia has been reported, but the role of androgen receptor (AR), a steroid receptor for testosterone, is not well understood. We have previously shown that peripheral inflammation upregulates μ-opioid receptor (MOR) in rat trigeminal ganglia (TG) in a testosterone-dependent manner. In this study, we hypothesized that testosterone regulates MOR expression via transcriptional activities of AR in TG. We first examined whether AR is co-expressed with MOR in TG neurons. Our immunohistochemical experiment revealed that AR staining is detected in neurons of all sizes in TG and that a subset of AR is expressed in MOR as well as in TRPV1-positive neurons. We identified the promoter region of the rat MOR gene contains putative AR binding sites. Using chromatin immunoprecipitation assay, we demonstrated that AR directly binds to these sites in TG extracts. We confirmed with luciferase reporter assay that AR activated the MOR promoter in response to androgens in a human neuroblastoma cell line (5H-5YSY). These data demonstrated that AR functions as a transcriptional regulator of the MOR gene activity. Finally, we showed that flutamide, a specific AR antagonist, prevents complete Freund's adjuvant (CFA)-induced upregulation of MOR mRNA in TG, and that flutamide dose-dependently blocks the efficacy of DAMGO, a specific MOR agonist, on CFA-induced mechanical hypersensitivity. Our results expand the knowledge regarding the role of androgens and their receptor in pain and analgesia and have important clinical implications, particularly for inflammatory pain patients with low or compromised plasma testosterone levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.