title: Ghrelin receptor agonist, GHRP-2, produces antinociceptive effects at the supraspinal level via the opioid receptor in mice.
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.
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Poyang Lake Environmental and Resource Utilization, Ministry of Education, School of Environmental and Chemical Engineering, Nanchang University, Nanchang, Jiangxi 330029, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.affiliation: Medical Experimental Teaching Department, Nanchang University, Nanchang 330031, China.
authors.forename: Yue-hui
authors.initials: YH
authors.lastname: Zheng
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China.
authors.forename: Fu-Yan
authors.initials: FY
authors.lastname: Liu
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China.
authors.forename: Jing-lei
authors.initials: JL
authors.lastname: Wang
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China.
authors.forename: Da-lei
authors.initials: DL
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China. Electronic address: jwei@ncu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
mesh_terms: D000700:Analgesics / Q000008:administration & dosage*; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D058748:Pain Perception / Q000187:drug effects; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000378:metabolism*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; C520836:GHRP-6, Lys(3)-; D009292:Narcotic Antagonists; D009842:Oligopeptides; D054440:Receptors, Ghrelin; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D009020:Morphine; C091874:growth hormone-releasing peptide-2
keywords: Antinociception; GHRP-2; Growth hormone secretagogue receptor 1 alpha (GHS-R1a); Morphine; Opioid receptor; Tail withdrawal test