{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:30:37Z","timestamp":1792657837270,"version":"4.5.0"},"reference-count":59,"publisher":"SAGE Publications","issue":"14","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008269","name":"L\u00e6ge Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013826","name":"Candys Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Knowledge of exact signalling events during migraine attacks is lacking. Various substances are known to trigger migraine attacks in patients and calcitonin gene-related peptide antagonising drugs are effective against migraine pain. Here, we investigated the signalling pathways involved in three different mouse models of provoked migraine and relate them to calcitonin gene-related peptide and other migraine-relevant targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo mouse models of glyceryl trinitrate-, cilostazol- and levcromakalim-induced migraine were applied utilising tactile sensitivity to von Frey filaments as measuring readout. Signalling pathways involved in the three models were dissected by use of specific knockout mice and chemical inhibitors. In vivo results were supported by ex vivo wire myograph experiments measuring arterial dilatory responses and ex vivo calcitonin gene-related peptide release from trigeminal ganglion and trigeminal nucleus caudalis from mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Glyceryl trinitrate-induced hypersensitivity was dependent on both prostaglandins and transient receptor potential cation channel, subfamily A, member 1, whereas cilostazol- and levcromakalim-induced hypersensitivity were independent of both. All three migraine triggers activated calcitonin gene-related peptide signalling, as both receptor antagonism and antibody neutralisation of calcitonin gene-related peptide were effective inhibitors of hypersensitivity in all three models. Stimulation of trigeminal ganglia and brain stem tissue samples with cilostazol and levcromakalim did not result in release of calcitonin gene-related peptide, and vasodilation following levcromakalim stimulation was independent of CGRP receptor antagonism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The mouse models of glyceryl trinitrate-, cilostazol- and levcromakalim- induced migraine all involve calcitonin gene-related peptide signalling in a complex interplay between different cell\/tissue types. These models are useful in the study of migraine mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024211038884","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T02:19:11Z","timestamp":1629339551000},"page":"1413-1426","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":49,"title":["CGRP-dependent signalling pathways involved in mouse models of GTN- cilostazol- and levcromakalim-induced migraine"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7985-4783","authenticated-orcid":false,"given":"Sarah L","family":"Christensen","sequence":"first","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke H","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-1902","authenticated-orcid":false,"given":"Charlotte","family":"Ernstsen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanne","family":"La Cour","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"David","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Chaker","sequence":"additional","affiliation":[{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-8957","authenticated-orcid":false,"given":"Kristian A","family":"Haanes","sequence":"additional","affiliation":[{"name":"Department of Clinical Experimental Research, Rigshospitalet Glostrup, Rigshospitalet Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren T","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Biology, Section of Cell Biology and Physiology, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes","family":"Olesen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark"},{"name":"Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en sant\u00e9, environnement et travail) - UMR_S 1085, Rennes, France"},{"name":"Department of Biology, Section of Cell Biology and Physiology, University of Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"bibr1-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1915327"},{"key":"bibr2-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00310.x"},{"key":"bibr3-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0003-1"},{"key":"bibr4-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419844711"},{"key":"bibr5-03331024211038884","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00233"},{"key":"bibr6-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2020.04.027"},{"key":"bibr7-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awu244"},{"key":"bibr8-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz199"},{"key":"bibr9-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.1994.tb00053.x"},{"key":"bibr10-03331024211038884","doi-asserted-by":"publisher","DOI":"10.3233\/VES-2012-0433"},{"key":"bibr11-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.137"},{"key":"bibr12-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417737778"},{"key":"bibr13-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy177"},{"key":"bibr14-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5381"},{"key":"bibr15-03331024211038884","doi-asserted-by":"crossref","unstructured":"Ito N, Ruegg UT, Kudo A, et\u00a0al. 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Targeting CGRP via receptor antagonism and antibody neutralisation in two distinct rodent models of migraine-like pain.\n                      Cephalalgia\n                      2019; 39: 1827\u20131837.","DOI":"10.1177\/0333102419861726"},{"key":"bibr28-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(94)90144-9"},{"key":"bibr29-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.20.040180.002301"},{"key":"bibr30-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.1528"},{"key":"bibr31-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102411430266"},{"key":"bibr32-03331024211038884","doi-asserted-by":"crossref","unstructured":"Ernstsen C, Christensen SL, Olesen J, et\u00a0al. No additive effect of combining sumatriptan and olcegepant in the GTN mouse model of migraine.\n                      Cephalalgia\n                      2021; 41: 329\u2013339.","DOI":"10.1177\/0333102420963857"},{"key":"bibr33-03331024211038884","doi-asserted-by":"publisher","DOI":"10.3758\/BF03207805"},{"key":"bibr34-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13164"},{"key":"bibr35-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413502735"},{"key":"bibr36-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102413517776"},{"key":"bibr37-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5381"},{"key":"bibr38-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-017-0804-4"},{"key":"bibr39-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7742(07)82020-4"},{"key":"bibr40-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.040832"},{"key":"bibr41-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102419844711"},{"key":"bibr42-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa003"},{"key":"bibr43-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)91549-T"},{"key":"bibr44-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244326"},{"key":"bibr45-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2010.00880.x"},{"key":"bibr46-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.07.026"},{"key":"bibr47-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2007.00871.x"},{"key":"bibr48-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102415584313"},{"key":"bibr49-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq159"},{"key":"bibr50-03331024211038884","doi-asserted-by":"crossref","unstructured":"Kuburas A, Mason BN, Hing B, et\u00a0al. PACAP induces light aversion in mice by an inheritable mechanism independent of CGRP.\n                      J Neurosci\n                      2021; 41: 4697\u20134715.","DOI":"10.1523\/JNEUROSCI.2200-20.2021"},{"key":"bibr51-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000001337"},{"key":"bibr52-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2016.04.004"},{"key":"bibr53-03331024211038884","first-page":"S16","volume":"43","author":"Moskowitz MA.","year":"1993","journal-title":"Neurology"},{"key":"bibr54-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1177\/0333102410363491"},{"key":"bibr55-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2982.2009.02014.x"},{"key":"bibr56-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.1997.1708873.x"},{"key":"bibr57-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy300"},{"key":"bibr58-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1111\/head.13634"},{"key":"bibr59-03331024211038884","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181f9626a"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024211038884","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024211038884","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024211038884","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:49:13Z","timestamp":1777387753000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03331024211038884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,18]]},"references-count":59,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1177\/03331024211038884"],"URL":"https:\/\/doi.org\/10.1177\/03331024211038884","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,18]]}}}