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)-1β 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.