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In this review, we aim to examine and discuss recent findings on the individual roles of MCs and the trigeminal nerve in migraine, as well as the various connections between their mechanisms with an emphasis on the contributions those relationships make to migraine. This is seen through MC release of histamine, among other compounds, and trigeminal nerve release of calcitonin-gene-related-peptide (CGRP) and pituitary adenylate cyclase activating peptide-38 (PACAP-38), which are peptides that are thought to contribute to migraine. Secondly, we illustrate the bi-directional relationship of neurogenic inflammation as well as highlight the role of MCs and their effect on the trigeminal nerve in migraine mechanisms. Lastly, we discuss potential new targets for clinical interventions of MC- and trigeminal nerve-mediated migraine, and present future perspectives of mechanistic and translational research.<\/jats:p>","DOI":"10.1177\/17448069231181358","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T03:47:14Z","timestamp":1685072834000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":44,"title":["Roles of mast cells and their interactions with the trigeminal nerve in migraine headache"],"prefix":"10.1177","volume":"19","author":[{"given":"Leo C","family":"Guan","sequence":"first","affiliation":[{"name":"McDonogh School, Owings Mills, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhong","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Johns Hopkins University, School of Medicine, Howard Hughes Medical Institute, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-1915","authenticated-orcid":false,"given":"Dustin P","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of Texas Medical Branch, Galveston, TX, 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