Spexin/NPQ Induces fos and Produces Antinociceptive Effect against Inflammatory Pain in the Mouse Model.

Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. This study explored the mechanisms and effects of supraspinal spexin on inflammatory pain. The results from the mouse formalin test show that intracerebroventricular (i.c.v.) administration of spexin decreased licking/biting time during the late and early phases. The non-amidated spexin had no effect on pain response. The antinociception of spexin was blocked by galanin receptor 3 antagonist SNAP 37889. The Galr3 and Adcy4 mRNA levels in the brain were increased after injection with spexin. The antinociceptive effects of spexin were completely reversed by opioid receptor antagonist naloxone and κ-opioid receptor antagonist nor-BNI. Spexin up-regulated the dynorphin and κ-opioid receptor gene and protein expression. PCR array assay and real-time PCR analysis show that spexin up-regulated mRNA level of Fos gene. T-5224, the inhibitor of c-Fos/AP-1, blocked the increased mRNA level of Pdyn and Oprk1 induced by spexin. Spexin (2.43 mg/kg, i.c.v.) increased the number of c-Fos-positive neurons in most subsection of periaqueductal gray. In addition, in the acetic acid-induced writhing test, i.c.v. spexin produced antinociceptive effect. Our results indicate that spexin might be a novel neuropeptide with antinociceptive effect against acute inflammatory pain.