Gonadal hormones decrease temporomandibular joint κ-mediated antinociception through a down-regulation in the expression of kappa opioid receptors in the trigeminal ganglia

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• 作者：Juliana T. Clemente-Napimoga ; Adriana Pellegrini-da-Silva ; Viní ; cius H.A. Ferreira ; Marcelo H. Napimoga ; Carlos A. Parada ; Clá ; udia H. Tambeli
• 关键词：class=""smCaps"">L-Arginine/NO/cGMP pathway ; Kappa opioid receptor ; Temporomandibular joint ; Sex difference ; Estrous cycle ; Nociception
• 刊名：European Journal of Pharmacology
• 出版年：2009
• 出版时间：1 September 2009
• 年：2009
• 卷：617
• 期：1-3
• 页码：41-47
• 全文大小：446 K

文摘

We have previously demonstrated that activation of κ-opioid receptor located in the temporomandibular joint (TMJ) of rats induces a significantly greater TMJ antinociception in diestrus females than in proestrus females (higher estradiol serum levels than diestrus) and males. These findings indicate that gonadal hormones decrease TMJ kappa-mediated antinociception. The aim of this study was to investigate some of the mechanisms by which gonadal hormones decrease TMJ kappa-mediated antinociception. Western blot analysis demonstrated a significantly lower κ-opioid receptor expression in the trigeminal ganglia of intact males than in intact and ovariechtomized (OVX) females and orchidectomized (ORX) males. In females, κ-opioid receptor expression in the trigeminal ganglia was significantly lower in proestrus than in diestrus and OVX females. Taken together these findings suggest that gonadal hormones, especially male gonadal hormones, down-regulate κ-opioid receptor expression. Co-application of the NOS inhibitor caps"">l-NMMA or the NO-sensitive guanylyl cyclase inhibitor ODQ with the κ-opioid receptor agonist U50,488 blocked TMJ kappa-mediated antinociception in males and females. These findings suggest that antinociception induced by activation of kappa opioid receptors in the TMJ region is mediated by the caps"">l-arginine/NO/cGMP pathway in both sexes. Despite the involvement of the caps"">l-arginine/NO/cGMP pathway in TMJ kappa-mediated antinociception in both sexes, gonadal hormones do not diminish the activity of this pathway to decrease TMJ kappa-mediated antinociception. Alternatively, they significantly reduce κ-opioid receptor expression in the trigeminal ganglia.