title: Activation of peripheral galanin receptors: differential effects on nociception.
abstract: Numerous reports suggest a significant role of peripheral galanin (GAL) in pain transmission; however, due to the lack of selective galanin receptor agonists and antagonists, the role of GAL receptors (GalR1-3) in pain transmission remains unclear. In this study, a new agonist, M617, that preferentially binds to GalR1, a GalR2 agonist (AR-M1896), and a GalR2 antagonist (M871) were tested in the periphery to elucidate the role of peripheral GalR1 and GalR2 in nociception. Ipsilateral, but not contralateral, hindpaw injection of M617 reduced capsaicin (CAP)-induced flinching by approximately 50%, suggesting that GalR1 activation produces anti-nociception. This anti-nociceptive effect was blocked by intraplantar injection of the non-selective GalR antagonist M35. In contrast ipsilateral, but not contralateral, intraplantar injection of GalR2 agonist AR-M1896 enhanced the CAP-induced nociception (1.7-fold). The GalR2 antagonist M871 blocked the pro-nociceptive effect of AR-M1896 in a dose-dependent manner. This antagonist had no effect on nociceptive behaviors induced by CAP alone. The data demonstrate that activation of peripheral GalR1 results in anti-nociception but activation of peripheral GalR2 produces pro-nociception. Thus, the use of these pharmacological tools may help to elucidate the contribution of GalR subtypes in nociceptive processing, identifying potential drug targets for the treatment of peripheral pain.
authors.affiliation: Seccion Externa de Farmacologia, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional, Av IPN 2508 San Pedro Zacatenco 07360, Mexico, DF Mexico.
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Jimenez-Andrade
authors.forename: Linda
authors.initials: L
authors.lastname: Lundström
authors.forename: Ulla E
authors.initials: UE
authors.lastname: Sollenberg
authors.forename: Ulo
authors.initials: U
authors.lastname: Langel
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernandez
authors.forename: Susan M
authors.initials: SM
authors.lastname: Carlton
mesh_terms: D000818:Animals; D008297:Male; D010146:Pain / Q000503:physiopathology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044088:Receptors, Galanin / Q000502:physiology*
chemical_list: C000603588:M871 peptide; D010455:Peptides; D044088:Receptors, Galanin