Activation of peripheral galanin receptors: Differential effects on nociception

Juan Miguel Jimenez-Andrade, Linda Lundström, Ulla E. Sollenberg, Ülo Langel, Gilberto Castañeda-Hernandez, Susan M. Carlton

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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 ∼ 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.

Original languageEnglish (US)
Pages (from-to)273-280
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume85
Issue number1
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • Anti-nociception
  • Capsaicin
  • Inflammatory pain
  • Primary afferent
  • Pro-nociception

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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