PMID- 23500519 OWN - NLM STAT- MEDLINE DCOM- 20140819 LR - 20130517 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 43 DP - 2013 May TI - In vivo characterization of the effects of ghrelin on the modulation of acute pain at the supraspinal level in mice. PG - 76-82 LID - S0196-9781(13)00078-8 [pii] LID - 10.1016/j.peptides.2013.03.004 [doi] AB - Ghrelin, an acylated peptide produced in the stomach, increases food intake and growth hormone secretion, inhibits pro-inflammatory cascade, etc. Ghrelin and its receptor (GHS-R1a) mRNA were found in the area related to the regions for controlling pain transmission, such as the hypothalamus, the midbrain, the spinal cord, etc. Ghrelin has been shown to have antinociceptive activity and also anti-inflammatory properties in inflammatory pain and chronic neuropathic pain. Therefore, the aim of the present study was to investigate the effects of ghrelin for the first time in the acute pain modulation at the supraspinal level, using the tail withdrawal test and hot-plate test in mice. Intracerebroventricular (i.c.v.) administration of ghrelin (mouse, 0.1-3 nmol) produced a dose- and time-related antinociceptive effect in the tail withdrawal test and hot-plate test, respectively. Antinociceptive effect elicited by ghrelin (i.c.v., 1 nmol) was significantly antagonized by opioid receptor antagonist naloxone (i.c.v., 10 nmol co-injection or i.p., 10mg/kg, 10 min prior to ghrelin) in both tail withdrawal test and hot-plate test. At these doses, naloxone significantly antagonized the antinociceptive effect induced by morphine (i.c.v., 3 nmol). Ghrelin (i.c.v., 1 nmol)-induced antinociception was significantly antagonized by co-injection with 10 nmol [d-Lys3]-GHRP-6, the selective antagonist of GHS-R1a identified more recently, while [d-Lys3]-GHRP-6 (10 nmol) alone induced neither hyperalgesia nor antinociception. Overall this data indicate that ghrelin could produce antinociception through an interaction with GHS-R1a and with the central opioid system. Thus ghrelin may be a promising peptide for developing new analgesic drugs. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Wei, Jie AU - Wei J AD - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China. jwei@ncu.edu.cn FAU - Zhi, Xing AU - Zhi X FAU - Wang, Xiao-Lang AU - Wang XL FAU - Zeng, Ping AU - Zeng P FAU - Zou, Ting AU - Zou T FAU - Yang, Bei AU - Yang B FAU - Wang, Jing-Lei AU - Wang JL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130314 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Ghrelin) SB - IM MH - Acute Pain/*drug therapy MH - Animals MH - Dose-Response Relationship, Drug MH - Ghrelin/administration & dosage/*pharmacology/*therapeutic use MH - Injections, Intraventricular MH - Mice MH - Mice, Inbred Strains MH - Spinal Cord/*drug effects/pathology EDAT- 2013/03/19 06:00 MHDA- 2014/08/20 06:00 CRDT- 2013/03/19 06:00 PHST- 2013/02/04 00:00 [received] PHST- 2013/03/04 00:00 [revised] PHST- 2013/03/04 00:00 [accepted] PHST- 2013/03/19 06:00 [entrez] PHST- 2013/03/19 06:00 [pubmed] PHST- 2014/08/20 06:00 [medline] AID - S0196-9781(13)00078-8 [pii] AID - 10.1016/j.peptides.2013.03.004 [doi] PST - ppublish SO - Peptides. 2013 May;43:76-82. doi: 10.1016/j.peptides.2013.03.004. Epub 2013 Mar 14.