PMID- 23801566 OWN - NLM STAT- MEDLINE DCOM- 20140904 LR - 20211021 IS - 1532-2149 (Electronic) IS - 1090-3801 (Print) IS - 1090-3801 (Linking) VI - 18 IP - 2 DP - 2014 Feb TI - Sex differences in mu-opioid receptor expression in trigeminal ganglia under a myositis condition in rats. PG - 151-61 LID - 10.1002/j.1532-2149.2013.00352.x [doi] AB - 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 mu-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. CI - (c) 2013 European Pain Federation - EFIC(R) FAU - Zhang, X AU - Zhang X AD - Department of Anesthesiology, Hospital of Stomatology, The First Affiliated Hospital, China Medical University, Shenyang, China. FAU - Zhang, Y AU - Zhang Y FAU - Asgar, J AU - Asgar J FAU - Niu, K Y AU - Niu KY FAU - Lee, J AU - Lee J FAU - Lee, K S AU - Lee KS FAU - Schneider, M AU - Schneider M FAU - Ro, J Y AU - Ro JY LA - eng GR - R01 DE019448/DE/NIDCR NIH HHS/United States GR - DE019448/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20130625 PL - England TA - Eur J Pain JT - European journal of pain (London, England) JID - 9801774 RN - 0 (Analgesics, Opioid) RN - 0 (Receptors, Opioid, mu) RN - 3XMK78S47O (Testosterone) SB - IM MH - Analgesics, Opioid/metabolism MH - Animals MH - Female MH - Humans MH - Inflammation/metabolism MH - Male MH - Myositis/drug therapy/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Opioid, mu/agonists/*metabolism MH - Sex Characteristics MH - Testosterone/administration & dosage/metabolism/pharmacology MH - Trigeminal Ganglion/drug effects/*metabolism MH - Up-Regulation PMC - PMC3916151 MID - NIHMS494095 COIS- Conflict of interest: There is no conflict of interest to declare. EDAT- 2013/06/27 06:00 MHDA- 2014/09/05 06:00 PMCR- 2015/02/01 CRDT- 2013/06/27 06:00 PHST- 2013/05/31 00:00 [accepted] PHST- 2013/06/27 06:00 [entrez] PHST- 2013/06/27 06:00 [pubmed] PHST- 2014/09/05 06:00 [medline] PHST- 2015/02/01 00:00 [pmc-release] AID - 10.1002/j.1532-2149.2013.00352.x [doi] PST - ppublish SO - Eur J Pain. 2014 Feb;18(2):151-61. doi: 10.1002/j.1532-2149.2013.00352.x. Epub 2013 Jun 25.