Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: Selective actions via GalR1 and GalR2 receptors

Galanin is a 29-aa neuropeptide with a complex role in pain processing. Sev eral galanin receptor subtypes are present in dorsal root ganglia and spina l cord with a differential distribution. Here, we describe a generation of a specific galanin R2 (GalR2) agonist, AR-M1896, and its application in stu dies of a rat neuropathic pain model (Bennett). The results show that in no rmal rats mechanical and cold allodynia of the hindpaw are induced after in trathecal infusion of low-dose galanin (25 ng per 0.5 mul/h). The same effe ct is seen with equimolar doses of AR-M1896 or AR-M961, an agonist both at GalR1 and GalR2 receptors. In allodynic Bennett model rats, the mechanical threshold increased dose-dependently after intrathecal injection of a high dose of AR-M961, whereas no effect was observed in the control or AR-M1896 group. No effect of either of the two compounds was observed in nonallodyni c Bennett model rats. These data indicate that a low dose of galanin has a nociceptive role at the spinal cord level mediated by GalR2 receptors, wher eas the antiallodynic effect of high-dose galanin on neuropathic pain is me diated by the GalR1 receptors. Thus, a selective GalR1 agonist may be used to treat neuropathic pain.