{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:54:04Z","timestamp":1792799644951,"version":"4.5.0"},"reference-count":62,"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":"Migr\u00e6nefonden"},{"DOI":"10.13039\/501100013826","name":"Candys Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BRIDGE \u2013 Translational Excellence Programme (bridge.ku.dk) at the Faculty of Health and Medical Sciences, University of Copenhagen, funded by the Novo Nordisk Foundation","award":["NNF20SA0064340"],"award-info":[{"award-number":["NNF20SA0064340"]}],"id":[{"id":"https:\/\/ror.org\/035b05819","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Torben og Alice Frimodts Fond and Ragna Rask-Nielsens Grundforskningsfond","id":[{"id":"https:\/\/ror.org\/02xs6yw09","id-type":"ROR","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>Migraine research has highlighted the pivotal role of nitric oxide (NO) in migraine pathophysiology. Nitric oxide donors such as glyceryl trinitrate (GTN) induce migraine attacks in humans, whereas spontaneous migraine attacks can be aborted by inhibiting NO production. The present study aimed to investigate how GTN triggers migraine through its three nitric oxide synthase (NOS) isoforms (neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS)) via a suspected feed-forward phenomenon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Migraine-relevant hypersensitivity was induced by repeated injection of GTN in an in vivo mouse model. Cutaneous tactile sensitivity was assessed using von Frey filaments. Signaling pathways involved in this model were dissected using non-selective and selective NOS inhibitors, knockout mice lacking eNOS or nNOS and their wild-type control mice. Also, we tested a soluble guanylate cyclase inhibitor and a peroxynitrite decomposition catalyst (N\n                      <jats:sub>total\u2009<\/jats:sub>\n                      =\u2009312).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Non-selective NOS inhibition blocked GTN-induced hypersensitivity. This response was partially associated with iNOS, and potentially nNOS and eNOS conjointly. Furthermore, we found that the GTN response was largely dependent on the generation of peroxynitrite and partly soluble guanylate cyclase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Migraine-relevant hypersensitivity induced by GTN is mediated by a possible feed-forward phenomenon of NO driven mainly by iNOS but with contributions from other isoforms. The involvement of peroxynitrite adds to the notion that oxidative stress reactions are also involved.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024241277542","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T11:12:42Z","timestamp":1727176362000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Mechanisms of GTN-induced migraine: Role of NOS isoforms, sGC and peroxynitrite in a migraine relevant mouse model"],"prefix":"10.1177","volume":"44","author":[{"given":"Charlotte","family":"Ernstsen","sequence":"first","affiliation":[{"name":"Department of Neurology, Danish Headache Center (TRACE), Copenhagen University Hospital \u2013 Rigshospitalet Glostrup, Copenhagen, Denmark"},{"name":"Translational Research Centre, Copenhagen University Hospital \u2013 Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Obelitz-Ryom","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center (TRACE), Copenhagen University Hospital \u2013 Rigshospitalet Glostrup, Copenhagen, Denmark"},{"name":"Translational Research Centre, Copenhagen University Hospital \u2013 Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M\u00f8bjerg B.","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Growth and Reproduction, Copenhagen University Hospital \u2013 Rigshospitalet Glostrup, Copenhagen, Denmark"},{"name":"Department of Science and Environment, Roskilde University, Roskilde, Denmark"},{"name":"University Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Sant\u00e9, Environnement Et Travail) \u2013 UMR_S, 1085, Rennes, \rFrance"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes","family":"Olesen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center (TRACE), Copenhagen University Hospital \u2013 Rigshospitalet Glostrup, Copenhagen, Denmark"},{"name":"Translational Research Centre, Copenhagen University Hospital \u2013 Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Louise","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center (TRACE), Copenhagen University Hospital \u2013 Rigshospitalet Glostrup, Copenhagen, Denmark"},{"name":"Translational Research Centre, Copenhagen University Hospital \u2013 Rigshospitalet, Glostrup, Denmark"},{"name":"Department of Anaesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, US"},{"name":"Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1168-165X","authenticated-orcid":false,"given":"Song","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center (TRACE), Copenhagen University Hospital \u2013 Rigshospitalet Glostrup, Copenhagen, Denmark"},{"name":"Translational Research Centre, Copenhagen University Hospital \u2013 Rigshospitalet, Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,9,24]]},"reference":[{"key":"bibr1-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30322-3"},{"key":"bibr2-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.137"},{"key":"bibr3-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.1994.tb00053.x"},{"key":"bibr4-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2013.10.004"},{"key":"bibr5-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)80021-9"},{"key":"bibr6-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26576"},{"key":"bibr7-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg009"},{"key":"bibr8-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199308000-00008"},{"key":"bibr9-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(94)00097-X"},{"key":"bibr10-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419861726"},{"key":"bibr11-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2009.01864.x"},{"key":"bibr12-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2008.01791.x"},{"key":"bibr13-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420963857"},{"key":"bibr14-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs306"},{"key":"bibr15-03331024241277542","doi-asserted-by":"publisher","DOI":"10.1177\/0333102415623070"},{"key":"bibr16-03331024241277542","first-page":"55","volume":"53","author":"Chaplan 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