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Recent progress, particularly through the human and animal provocation model, has deepened our understanding of its mechanisms. This model have identified endogenous neuropeptides such as calcitonin gene\u2010related peptide (CGRP) and pituitary adenylate cyclase\u2010activating peptide (PACAP) that induces controlled migraine\u2010like attacks leading to significant discoveries of their role in migraine. This knowledge led to the development of CGRP\u2010inhibiting drugs; a groundbreaking migraine treatment now accessible globally. Also a PACAP\u2010inhibiting drug was effective in a recent phase II trial. Notably, rodent studies have shed light on pain pathways and the mechanisms of various migraine\u2010inducing substances identifying novel drug targets. This is primarily done by using selective inhibitors that target specific signaling pathways of the known migraine triggers leading to the hypothesized cellular cascade model of migraine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The model of migraine presents numerous opportunities for innovative drug development. The future of new migraine treatments is limited only by the investment from pharmaceutical companies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16333","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T05:55:50Z","timestamp":1718776550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Molecular nociceptive mechanisms in migraine: The migraine cascade"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1168-165X","authenticated-orcid":false,"given":"Song","family":"Guo","sequence":"first","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Translational Research Center, Rigshospitalet\u2010Glostrup, Faculty of Health and Medical Sciences University of Copenhagen  Glostrup Denmark"},{"name":"Department of Neurology Zealand University Hospital  Roskilde Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Louise","family":"Christensen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Translational Research Center, Rigshospitalet\u2010Glostrup, Faculty of Health and Medical Sciences University of Copenhagen  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Al\u2010Mahdi","family":"Al\u2010Karagholi","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Translational Research Center, Rigshospitalet\u2010Glostrup, Faculty of Health and Medical Sciences University of Copenhagen  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-2702","authenticated-orcid":false,"given":"Jes","family":"Olesen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology, Translational Research Center, Rigshospitalet\u2010Glostrup, Faculty of Health and Medical Sciences University of Copenhagen  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/S10194-020-01208-0"},{"key":"e_1_2_13_3_1","unstructured":"NIH Research Portfolio Online Reporting Tools (RePORT).Report on NIH funding vs. global burden of disease.https:\/\/report.nih.gov\/report\u2010nih\u2010funding\u2010vs\u2010global\u2010burden\u2010disease"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2006.05116.x"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2011.03612.x"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13275"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.137"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90075-2"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00310.x"},{"key":"e_1_2_13_10_1","unstructured":"H. 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