Sexual Dimorphism in the Antinociception Mediated by Kappa Opioid Receptors in the Rat Temporomandibular Joint

This study assessed the effect of the kappa opioid receptor agonist U50,488 administered into the rat temporomandibular joint (TMJ) on nociceptive behavioral responses evoked by formalin injected into the same site. Groups consisted of females, stratified into proestrus and diestrus phases of the estrous cycle, and males. Intra-TMJ formalin induced significantly different dose-dependent responses among the three groups, with diestrus females showing greater responses than males or proestrus females; therefore, equi-nociceptive formalin doses were chosen to test the effects of U50,488. U50,488 significantly reduced formalin-induced nociceptive behavior in all groups, but the reduction was significantly greater in females, especially those in diestrus. Pre-injection of the selective kappa opioid receptor antagonist nor-binaltorphimine (nor-BNI) into the same site significantly attenuated the effect of U50488; U50,488 injection into the contralateral TMJ failed to reduce nociceptive behavior. These findings support a role for kappa opioid receptors local to the site of inflammation to modulate inflammatory pain. Furthermore, since plasma levels of ovarian hormones are low during diestrus, these findings are consistent with the suggestion that sex hormones may play an antagonistic role in these peripheral kappa-mediated effects.