Ghrelin receptor agonist, GHRP-2, produces antinociceptive effects at the supraspinal level via the opioid receptor in mice

Peptides. 2014 May:55:103-9. doi: 10.1016/j.peptides.2014.02.013. Epub 2014 Mar 4.

Abstract

GHRP-2 is a synthetic agonist of ghrelin receptor. GHRP-2 has similar physiological functions with ghrelin. In our previous study, ghrelin (i.c.v.) could induce analgesic effect through an interaction with GHS-R1α and with the central opioid system in the acute pain in mice. To date, the function of GHRP-2 in pain processing was not understood. Therefore the aim of this study was to investigate the effects of GHRP-2 on pain modulation at supraspinal level in mice using the tail immersion test. Intracerebroventricular (i.c.v.) administration of GHRP-2 (0.1, 0.3, 1, 3 and 10 nmol/L) produced a concentration- and time-related antinociceptive effect. This effect could be fully antagonized by GHS-R1α antagonist [d-Lys(3)]-GHRP-6, indicating that the analgesic effect induced by GHRP-2 is mediated through the activation of GHS-R1α. Interestingly, naloxone, naltrindole and nor-binaltorphimine, but not β-funaltrexamine, could also block the analgesic effect markedly, suggesting that δ- and κ-opioid receptor is involved in the analgesic response evoked by GHRP-2. Moreover, i.c.v. administration of GHRP-2 potentiated the analgesic effect induced by morphine (i.c.v., 1 nmol/L) and this potentiated effect could not be reversed by [d-Lys(3)]-GHRP-6. Thus these findings may be a new strategy on investigating the interaction between ghrelin system and opioids on pain modulation. Furthermore, GHRP-2 may be a promising peptide for developing new analgesic drugs.

Keywords: Antinociception; GHRP-2; Growth hormone secretagogue receptor 1 alpha (GHS-R1a); Morphine; Opioid receptor; Tail withdrawal test.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage*
  • Analgesics, Opioid / administration & dosage
  • Animals
  • Injections, Intraventricular
  • Male
  • Mice
  • Morphine / administration & dosage
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Oligopeptides / administration & dosage*
  • Oligopeptides / pharmacology
  • Pain Perception / drug effects
  • Receptors, Ghrelin / antagonists & inhibitors
  • Receptors, Opioid, delta / metabolism*
  • Receptors, Opioid, kappa / metabolism*

Substances

  • Analgesics
  • Analgesics, Opioid
  • GHRP-6, Lys(3)-
  • Narcotic Antagonists
  • Oligopeptides
  • Receptors, Ghrelin
  • Receptors, Opioid, delta
  • Receptors, Opioid, kappa
  • Naloxone
  • Morphine
  • growth hormone-releasing peptide-2