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

doi:10.1073/pnas.161293598

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

^*Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden; and ^†AstraZeneca R & D Montreal, Ville Satin-Laurient, Montreal, QC, Canada H4S 1Z9

Contributed by Tomas Hökfelt

Abstract

Galanin is a 29-aa neuropeptide with a complex role in pain processing. Several galanin receptor subtypes are present in dorsal root ganglia and spinal cord with a differential distribution. Here, we describe a generation of a specific galanin R2 (GalR2) agonist, AR-M1896, and its application in studies of a rat neuropathic pain model (Bennett). The results show that in normal rats mechanical and cold allodynia of the hindpaw are induced after intrathecal infusion of low-dose galanin (25 ng per 0.5 μl/h). The same effect 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 nonallodynic 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, whereas the antiallodynic effect of high-dose galanin on neuropathic pain is mediated by the GalR1 receptors. Thus, a selective GalR1 agonist may be used to treat neuropathic pain.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: Tomas.Hokfelt{at}neuro.ki.se.
Abbreviations:

GalR1-R and GalR2-R,

galanin R1 and R2 receptors;

i.t.,

intrathecal;

DRG,

dorsal root ganglia;

h,

human;

r,

rat