PMID- 22940464 OWN - NLM STAT- MEDLINE DCOM- 20130715 LR - 20220321 IS - 1872-6623 (Electronic) IS - 0304-3959 (Print) IS - 0304-3959 (Linking) VI - 153 IP - 11 DP - 2012 Nov TI - Effects of gonadal hormones on the peripheral cannabinoid receptor 1 (CB1R) system under a myositis condition in rats. PG - 2283-2291 LID - 10.1016/j.pain.2012.07.037 [doi] AB - In this study, we assessed the effects of peripherally administered cannabinoids in an orofacial myositis model, and the role of sex hormones in cannabinoid receptor (CBR) expression in trigeminal ganglia (TG). Peripherally administered arachidonylcyclopropylamide (ACPA), a specific CB1R agonist, significantly attenuated complete Freund's adjuvant (CFA)-induced mechanical hypersensitivity in the masseter muscle in male rats. The ACPA effect was blocked by a local administration of AM251, a specific CB1R antagonist, but not by AM630, a specific CB2R antagonist. In female rats, a 30-fold higher dose of ACPA was required to produce a moderate reduction in mechanical hypersensitivity. CFA injected in masseter muscle significantly upregulated CB1R mRNA expression in TG in male, but not in female, rats. There was a close correlation between the CB1R mRNA levels in TG and the antihyperalgesic effect of ACPA. Interleukin (IL)-1beta and IL-6, which are elevated in the muscle tissue following CFA treatment, induced a significant upregulation of CB1R mRNA expression in TG from male rats. The upregulation of CB1R was prevented in TG cultures from orchidectomized male rats, which was restored by the application of testosterone. The cytokines did not alter the CB1R mRNA level in TG from intact as well as ovariectomized female rats. Neither estradiol supplement nor estrogen receptor blockade had any effects on CB1R expression. These data indicate that testosterone, but not estradiol, is required for the regulation of CB1Rs in TG under inflammatory conditions, which provide explanations for the sex differences in the antihyperalgesic effects of peripherally administered cannabinoids. CI - Copyright (c) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. FAU - Niu, Katelyn Y AU - Niu KY AD - Program in Neuroscience, Department of Neural and Pain Sciences, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. FAU - Zhang, Youping AU - Zhang Y FAU - Ro, Jin Y AU - Ro JY LA - eng GR - F30 DE020988/DE/NIDCR NIH HHS/United States GR - R01 DE019448/DE/NIDCR NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120831 PL - United States TA - Pain JT - Pain JID - 7508686 RN - 0 (Cnr2 protein, rat) RN - 0 (Estrogens) RN - 0 (Receptor, Cannabinoid, CB1) RN - 0 (Receptor, Cannabinoid, CB2) RN - 3XMK78S47O (Testosterone) SB - IM MH - Animals MH - Disease Models, Animal MH - Estrogens/*physiology MH - Facial Pain/drug therapy/*physiopathology MH - Female MH - Male MH - Myositis/drug therapy/*physiopathology MH - Primary Cell Culture MH - Rats MH - Rats, Sprague-Dawley MH - Receptor, Cannabinoid, CB1/agonists/antagonists & inhibitors/*genetics MH - Receptor, Cannabinoid, CB2/agonists/antagonists & inhibitors/physiology MH - Testosterone/*physiology PMC - PMC3578305 MID - NIHMS399508 EDAT- 2012/09/04 06:00 MHDA- 2013/07/17 06:00 PMCR- 2013/11/01 CRDT- 2012/09/04 06:00 PHST- 2012/03/19 00:00 [received] PHST- 2012/07/31 00:00 [revised] PHST- 2012/07/31 00:00 [accepted] PHST- 2012/09/04 06:00 [entrez] PHST- 2012/09/04 06:00 [pubmed] PHST- 2013/07/17 06:00 [medline] PHST- 2013/11/01 00:00 [pmc-release] AID - 00006396-201211000-00020 [pii] AID - 10.1016/j.pain.2012.07.037 [doi] PST - ppublish SO - Pain. 2012 Nov;153(11):2283-2291. doi: 10.1016/j.pain.2012.07.037. Epub 2012 Aug 31.