Chronic activation of sigma-1 receptor evokes nociceptive activation of trigeminal nucleus caudalis in rats

摘要

Primary headache disorders, including migraine, are thought to be mediated by prolonged nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. Our past studies demonstrated that sigma-1 receptors (Sig-IR) facilitate spinal nociceptive transmission in several pain models. Based on these findings, this study asked if chronic activation of Sig-1 R by intracisternal administration of the selective Sig-1 R agonist, PRE084, produced TNC neuronal activation as a migraine trigger in rats. A single infusion of PRE084 (10,50,100,500 nmol) significantly increased the number of Fos immunoreactive neurons (Fos-IR) in TNC, which BD1047 (a Sig-IR antagonist) reversed. Chronic infusion of PRE084 (100 nmol for 1, 3, 7 and 14 days) time-dependently elevated Fos-IR in TNC.