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

Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9960-4. doi: 10.1073/pnas.161293598. Epub 2001 Jul 31.

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 microl/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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Non-Narcotic / administration & dosage
  • Analgesics, Non-Narcotic / pharmacology
  • Analgesics, Non-Narcotic / therapeutic use*
  • Animals
  • Causalgia / chemically induced
  • Causalgia / drug therapy
  • Causalgia / physiopathology*
  • Cold Temperature / adverse effects
  • Dose-Response Relationship, Drug
  • Galanin / administration & dosage
  • Galanin / chemistry
  • Galanin / pharmacology*
  • Galanin / physiology*
  • Galanin / therapeutic use
  • Galanin / toxicity
  • Ganglia, Spinal / chemistry
  • Ganglia, Spinal / drug effects
  • Hindlimb / innervation
  • Hyperesthesia / chemically induced
  • Hyperesthesia / drug therapy
  • Hyperesthesia / etiology
  • Hyperesthesia / physiopathology*
  • Infusion Pumps, Implantable
  • Male
  • Models, Animal
  • Nerve Tissue Proteins / agonists
  • Nerve Tissue Proteins / physiology*
  • Pain Threshold / drug effects
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Protein Isoforms / agonists
  • Protein Isoforms / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Galanin
  • Receptors, Neuropeptide / agonists
  • Receptors, Neuropeptide / physiology*
  • Sciatic Nerve / injuries
  • Sciatica / drug therapy
  • Sciatica / etiology
  • Sciatica / physiopathology*
  • Spinal Cord / chemistry
  • Spinal Cord / physiopathology*
  • Stress, Mechanical
  • Substrate Specificity

Substances

  • Analgesics, Non-Narcotic
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Protein Isoforms
  • Receptors, Galanin
  • Receptors, Neuropeptide
  • galanin (1-11)-amide
  • galanin (1-16)-amide, Sar(1)-Ala(12)-
  • galanin (2-11)-amide
  • Galanin