PMID- 24607724 OWN - NLM STAT- MEDLINE DCOM- 20141218 LR - 20161125 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 55 DP - 2014 May TI - Ghrelin receptor agonist, GHRP-2, produces antinociceptive effects at the supraspinal level via the opioid receptor in mice. PG - 103-9 LID - S0196-9781(14)00057-6 [pii] LID - 10.1016/j.peptides.2014.02.013 [doi] AB - 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-R1alpha 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-R1alpha antagonist [d-Lys(3)]-GHRP-6, indicating that the analgesic effect induced by GHRP-2 is mediated through the activation of GHS-R1alpha. Interestingly, naloxone, naltrindole and nor-binaltorphimine, but not beta-funaltrexamine, could also block the analgesic effect markedly, suggesting that delta- and kappa-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. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Zeng, Ping AU - Zeng P AD - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China. FAU - Li, Shu AU - Li S AD - Key Laboratory of Poyang Lake Environmental and Resource Utilization, Ministry of Education, School of Environmental and Chemical Engineering, Nanchang University, Nanchang, Jiangxi 330029, China. FAU - Zheng, Yue-hui AU - Zheng YH AD - Medical Experimental Teaching Department, Nanchang University, Nanchang 330031, China. FAU - Liu, Fu-Yan AU - Liu FY AD - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China. FAU - Wang, Jing-lei AU - Wang JL AD - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China. FAU - Zhang, Da-lei AU - Zhang DL AD - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China. FAU - Wei, Jie AU - Wei J AD - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China. Electronic address: jwei@ncu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140304 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Analgesics) RN - 0 (Analgesics, Opioid) RN - 0 (GHRP-6, Lys(3)-) RN - 0 (Narcotic Antagonists) RN - 0 (Oligopeptides) RN - 0 (Receptors, Ghrelin) RN - 0 (Receptors, Opioid, delta) RN - 0 (Receptors, Opioid, kappa) RN - 36B82AMQ7N (Naloxone) RN - 76I7G6D29C (Morphine) RN - E6S6E1F19M (growth hormone-releasing peptide-2) SB - IM MH - Analgesics/*administration & dosage MH - Analgesics, Opioid/administration & dosage MH - Animals MH - Injections, Intraventricular MH - Male MH - Mice MH - Morphine/administration & dosage MH - Naloxone/pharmacology MH - Narcotic Antagonists/pharmacology MH - Oligopeptides/*administration & dosage/pharmacology MH - Pain Perception/drug effects MH - Receptors, Ghrelin/antagonists & inhibitors MH - Receptors, Opioid, delta/*metabolism MH - Receptors, Opioid, kappa/*metabolism OTO - NOTNLM OT - Antinociception OT - GHRP-2 OT - Growth hormone secretagogue receptor 1 alpha (GHS-R1a) OT - Morphine OT - Opioid receptor OT - Tail withdrawal test EDAT- 2014/03/13 06:00 MHDA- 2014/12/19 06:00 CRDT- 2014/03/11 06:00 PHST- 2014/01/10 00:00 [received] PHST- 2014/02/20 00:00 [revised] PHST- 2014/02/20 00:00 [accepted] PHST- 2014/03/11 06:00 [entrez] PHST- 2014/03/13 06:00 [pubmed] PHST- 2014/12/19 06:00 [medline] AID - S0196-9781(14)00057-6 [pii] AID - 10.1016/j.peptides.2014.02.013 [doi] PST - ppublish SO - Peptides. 2014 May;55:103-9. doi: 10.1016/j.peptides.2014.02.013. Epub 2014 Mar 4.