{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:54:56Z","timestamp":1793058896629,"version":"4.5.0"},"reference-count":46,"publisher":"Society for Neuroscience","issue":"41","license":[{"start":{"date-parts":[[2012,4,12]],"date-time":"2012-04-12T00:00:00Z","timestamp":1334188800000},"content-version":"vor","delay-in-days":183,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2011,10,12]]},"abstract":"<jats:p>\n                    Orexin A and B are hypothalamic peptides known to modulate arousal, feeding, and reward via OX\n                    <jats:sub>1<\/jats:sub>\n                    and OX\n                    <jats:sub>2<\/jats:sub>\n                    receptors. Orexins are also antinociceptive in the brain, but their mechanism(s) of action remain unclear. Here, we investigated the antinociceptive mechanism of orexin A in the rat ventrolateral periaqueductal gray (vlPAG), a midbrain region crucial for initiating descending pain inhibition. In vlPAG slices, orexin A (30\u2013300 n\n                    <jats:sc>m<\/jats:sc>\n                    ) depressed GABAergic evoked IPSCs. This effect was blocked by an OX\n                    <jats:sub>1<\/jats:sub>\n                    [1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea (SB 334867)], but not OX\n                    <jats:sub>2<\/jats:sub>\n                    [\n                    <jats:italic>N<\/jats:italic>\n                    -acyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline hydrochloride (compound 29)], antagonist. Orexin A increased the paired-pulse ratio of paired IPSCs and decreased the frequency, but not amplitude, of miniature IPSCs. Orexin A-induced IPSC depression was mimicked by (\n                    <jats:italic>R<\/jats:italic>\n                    )-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-\n                    <jats:italic>de<\/jats:italic>\n                    ]-1,4-benzoxazin-6-yl]-1-napthalenylmethanone (WIN 55,212-2), a cannabinoid 1 (CB\n                    <jats:sub>1<\/jats:sub>\n                    ) receptor agonist. 1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-\n                    <jats:italic>N<\/jats:italic>\n                    -(1-piperidyl)pyrazole-3-carboxamide (AM 251), a CB\n                    <jats:sub>1<\/jats:sub>\n                    antagonist, reversed depressant effects by both agonists. Orexin A-induced IPSC depression was prevented by 1-[6-[[(17\u03b2)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1\n                    <jats:italic>H<\/jats:italic>\n                    -pyrrole-2,5-dione (U73122) and tetrahydrolipstatin, inhibitors of phospholipase C (PLC) and diacylglycerol lipase (DAGL), respectively, and enhanced by cyclohexyl[1,1\u2032-biphenyl]-3-ylcarbamate (URB602), which inhibits enzymatic degradation of 2-arachidonoylglycerol (2-AG). Moderate DAGL\u03b1, but not DAGL\u03b2, immunoreactivity was observed in the vlPAG. Orexin A produced an overall excitatory effect on evoked postsynaptic potentials and hence increased vlPAG neuronal activity. Intra-vlPAG microinjection of orexin A reduced hot-plate nociceptive responses in rats in a manner blocked by SB 334867 and AM 251. Therefore, orexin A may produce antinociception by activating postsynaptic OX\n                    <jats:sub>1<\/jats:sub>\n                    receptors, stimulating synthesis of 2-AG, an endocannabinoid, through a Gq-protein-mediated PLC\u2013DAGL\u03b1 enzymatic cascade culminating in retrograde inhibition of GABA release (disinhibition) in the vlPAG.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2671-11.2011","type":"journal-article","created":{"date-parts":[[2011,10,12]],"date-time":"2011-10-12T13:02:13Z","timestamp":1318424533000},"page":"14600-14610","source":"Crossref","is-referenced-by-count":157,"title":["Activation of Orexin 1 Receptors in the Periaqueductal Gray of Male Rats Leads to Antinociception via Retrograde Endocannabinoid (2-Arachidonoylglycerol)-Induced Disinhibition"],"prefix":"10.1523","volume":"31","author":[{"given":"Yu-Cheng","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Jung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wei","family":"Tung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Yu","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu-Ying","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Fang","family":"Teng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Tzu","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Mackie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lih-Chu","family":"Chiou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2011,10,12]]},"reference":[{"key":"2023041303525872000_31.41.14600.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2010.09.006"},{"key":"2023041303525872000_31.41.14600.2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(90)90070-T"},{"key":"2023041303525872000_31.41.14600.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2007.11.006"},{"key":"2023041303525872000_31.41.14600.4","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/S0022-3565(25)22967-6","article-title":"Selective 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