{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:13:47Z","timestamp":1790702027258,"version":"4.1.0"},"reference-count":70,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"U.S. Department of Defense","award":["PR230220"],"award-info":[{"award-number":["PR230220"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 NS120395"],"award-info":[{"award-number":["R01 NS120395"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 NS129552"],"award-info":[{"award-number":["R01 NS129552"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We wished to explore possible sexual dimorphism in mechanisms sensitizing or activating meningeal nociceptors that can promote the headache phase of migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female C57BL6J mice received either supradural orexin B and an inflammatory mediator cocktail (IM) with migraine-like pain behaviors and photophobia recorded. Expression of orexin 2 receptor (OX2R) in trigeminal ganglion (TG) and phosphorylated extracellular signal-regulated kinases (ERK) levels in trigeminal nucleus caudalis (TNC) were evaluated. Orexin B-induced excitability of TG cells was assessed with patch-clamp electrophysiology. Intranasal delivery of CRISPR\/Cas9 plasmids was used to edit the expression of OX2R in the TG.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Supradural orexin B induced migraine-like pain behaviors, photophobia and increased TNC ERK phosphorylation exclusively in males. Blockade of orexin signaling with supradural suvorexant, a dual orexin receptor antagonist, prevented, but did not reverse, migraine-like pain in males induced by supradural IM cocktail. OX2R expression was higher in male TG and orexin B increased TG neuron excitability in males. Intranasal OX2R CRISPR\/Cas9 reduced TG receptor expression and orexin B-induced TNC ERK phosphorylation and prevented migraine-like pain induced by supradural orexin B in males.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our studies reveal a male-specific mechanism of TG nociceptor sensitization and migraine-like pain behavior mediated by orexin B\/OX2R signaling. Sexually dimorphic mechanisms of trigeminal nociceptor sensitization and activation offer opportunities to improve patient outcomes by considering patient sex and may influence clinical trial design and interpretation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024241281493","type":"journal-article","created":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T00:29:48Z","timestamp":1725668988000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":18,"title":["A male-specific mechanism of meningeal nociceptor sensitization promoting migraine headache"],"prefix":"10.1177","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5392-5117","authenticated-orcid":false,"given":"Caroline M.","family":"Kopruszinski","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent K.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA"},{"name":"Department of Anesthesiology, University of Arizona College of Medicine, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara R.","family":"Barber","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubin","family":"Moutal","sequence":"additional","affiliation":[{"name":"Pharmacology and Physiology, Saint Louis University, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Dodick","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ, USA"},{"name":"Atria Academy of Science and Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edita","family":"Navratilova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA"},{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-0617","authenticated-orcid":false,"given":"Frank","family":"Porreca","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ, USA"},{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"bibr1-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32160-7"},{"key":"bibr2-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00763-1"},{"key":"bibr3-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1111\/head.14389"},{"key":"bibr4-03331024241281493","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/head.14109","volume":"62","author":"Mullin K","year":"2022","journal-title":"Headache"},{"key":"bibr5-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0364-19.2019"},{"key":"bibr6-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42843"},{"key":"bibr7-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/03331024211039813"},{"key":"bibr8-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002835"},{"key":"bibr9-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72285-z"},{"key":"bibr10-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac266"},{"key":"bibr11-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-31603-x"},{"key":"bibr12-03331024241281493","author":"Stratton H","year":"2023","journal-title":"BioRxiv"},{"key":"bibr13-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.09.022"},{"key":"bibr14-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac104"},{"key":"bibr15-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.2335"},{"key":"bibr16-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/03331024241238153"},{"key":"bibr17-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1007\/s00391-018-01461-8"},{"key":"bibr18-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2301951120"},{"key":"bibr19-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.107993"},{"key":"bibr20-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80949-6"},{"key":"bibr21-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1159\/000514963"},{"key":"bibr22-03331024241281493","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00220"},{"key":"bibr23-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-012-1297-4"},{"key":"bibr24-03331024241281493","doi-asserted-by":"publisher","DOI":"10.2174\/138161210793292483"},{"key":"bibr25-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.00842.x"},{"key":"bibr26-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1111\/head.13078"},{"key":"bibr27-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1515\/biol-2021-0001"},{"key":"bibr28-03331024241281493","doi-asserted-by":"publisher","DOI":"10.2174\/0929867324666170529072554"},{"key":"bibr29-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2024.2328728"},{"key":"bibr30-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2014.03.043"},{"key":"bibr31-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01195-2"},{"key":"bibr32-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00033-1"},{"key":"bibr33-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418786261"},{"key":"bibr34-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-08-03171.1999"},{"key":"bibr35-03331024241281493","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00132"},{"key":"bibr36-03331024241281493","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.155496"},{"key":"bibr37-03331024241281493","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.1070522"},{"key":"bibr38-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0264386"},{"key":"bibr39-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420959794"},{"key":"bibr40-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420966581"},{"key":"bibr41-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.06.012"},{"key":"bibr42-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-0963-6"},{"key":"bibr43-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/1744806919867842"},{"key":"bibr44-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418779557"},{"key":"bibr45-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp184"},{"key":"bibr46-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109121"},{"key":"bibr47-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2021.05.006"},{"key":"bibr48-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-019-1043-7"},{"key":"bibr49-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26070"},{"key":"bibr50-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay7550"},{"key":"bibr51-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1111\/head.13300"},{"key":"bibr52-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra010917"},{"key":"bibr53-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418771350"},{"key":"bibr54-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.029"},{"key":"bibr55-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2004.02.005"},{"key":"bibr56-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05168.x"},{"key":"bibr57-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.03.053"},{"key":"bibr58-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.090951"},{"key":"bibr59-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2001.013120"},{"key":"bibr60-03331024241281493","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.931739"},{"key":"bibr61-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.8.8299"},{"key":"bibr62-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1002\/cne.1190"},{"key":"bibr63-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-12601-x"},{"key":"bibr64-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.10.013"},{"key":"bibr65-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(02)00052-9"},{"key":"bibr66-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01030-3"},{"key":"bibr67-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-0030"},{"key":"bibr68-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(98)00977-X"},{"key":"bibr69-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01336-0"},{"key":"bibr70-03331024241281493","doi-asserted-by":"publisher","DOI":"10.1177\/0333102414544979"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024241281493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024241281493","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024241281493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:46:30Z","timestamp":1777387590000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03331024241281493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":70,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1177\/03331024241281493"],"URL":"https:\/\/doi.org\/10.1177\/03331024241281493","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"article-number":"03331024241281493"}}