{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:31:44Z","timestamp":1777386704688,"version":"3.51.4"},"reference-count":46,"publisher":"Canadian Science Publishing","issue":"10","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":["cdnsciencepub.com"],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p> G (1-5)-NH<jats:sub>2<\/jats:sub>, G (1-7)-NH<jats:sub>2<\/jats:sub>, and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood\u2013brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol\/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60\u00a0min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain\u2013blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1\u03b1 antagonist [D-Lys<jats:sup>3<\/jats:sup>]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1\u03b1. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain\u2013blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1\u03b1 after intravenous injection. <\/jats:p>","DOI":"10.1139\/cjpp-2020-0668","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T22:20:16Z","timestamp":1631053216000},"page":"1057-1068","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The active fragments of ghrelin cross the blood\u2013brain barrier and enter the brain to produce antinociceptive effects after systemic administration"],"prefix":"10.1139","volume":"99","author":[{"given":"Bao-wei","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-ling","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gui-xian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-xiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren-wen","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi, 330006, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.102.034827"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2008.07.001"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1177\/0023677218824382"},{"issue":"9","key":"refg4\/ref4","doi-asserted-by":"crossref","first-page":"984","DOI":"10.56093\/ijans.v82i9.23650","volume":"82","author":"Chandra V.","year":"2012","journal-title":"Indian J. 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