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Meanwhile, the ventral tegmental area (VTA), as a part of descending pain inhibitory system, responds to noxious stimuli. This study aimed to investigate the role of intra\u2010VTA administration of orexin receptor antagonists on stress\u2010induced antinociceptive responses in the animal model of acute pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Ninety\u2010three adult Wistar rats weighing 230\u2013250\u00a0g were unilaterally implanted by a cannulae above the VTA. Animals were pretreated with different doses (1, 3, 10 and 30\u00a0nM\/0.3\u00a0\u03bcl) of SB334867 as the orexin\u20101 receptor antagonist and TCS OX2 29 as the orexin\u20102 receptor antagonist into the VTA, just 5\u00a0min before 6\u00a0min exposure to forced swim stress (FSS). Nociceptive threshold was measured using the tail\u2010flick test as a model of acute pain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that exposure to FSS could significantly increase analgesic responses. Moreover, intra\u2010VTA administration of SB334768 and TCS OX2 29 blocked the antinociceptive effect of FSS in the tail\u2010flick test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The findings suggest that OX1 and OX2 receptors in the VTA might modulate the antinociceptive behaviours induced by FSS in part.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Acute exposure to physical stress suppresses pain\u2010related behaviors in the animal model of acute pain. Blockade of the OX1 and OX2 receptors in the VTA attenuates antinociceptive responses induced by FSS. The contribution of the OX2 receptors in the VTA is more predominant than OX1 receptors in stress\u2010induced analgesia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1840","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T08:36:55Z","timestamp":1626770215000},"page":"2266-2277","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Modulatory role of the orexin system in stress\u2010induced analgesia: Involvement of the ventral tegmental area"],"prefix":"10.1002","volume":"25","author":[{"given":"Kobra","family":"Askari","sequence":"first","affiliation":[{"name":"Department of Animal Biology Faculty of Biological Science Kharazmi University Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrbanoo","family":"Oryan","sequence":"additional","affiliation":[{"name":"Department of Animal Biology Faculty of Biological Science Kharazmi University Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram","family":"Eidi","sequence":"additional","affiliation":[{"name":"Department of Biology, Science and Research Branch Islamic Azad University Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalal","family":"Zaringhalam","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1084-180X","authenticated-orcid":false,"given":"Abbas","family":"Haghparast","sequence":"additional","affiliation":[{"name":"Neuroscience Research Center School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(96)00121\u20107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031\u20109384(98)00246\u20107"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.08.010"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.09.106"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.07.012"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/306791a0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102414562971"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.09.019"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304\u20103959(00)00470\u2010X"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811507106"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(07)61305\u20101"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2009.04.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2006.11.009"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.106"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300934"},{"issue":"1","key":"e_1_2_7_17_1","first-page":"74","article-title":"A method for determining loss of pain sensation","volume":"72","author":"D'amour F. 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