{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:04:27Z","timestamp":1791266667856,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R345\u20102020\u20101977"],"award-info":[{"award-number":["R345\u20102020\u20101977"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The transient receptor potential melastatin 3 (TRPM3) ion channel has been implicated in sensory modulation and pain transmission and may contribute to migraine pathophysiology through calcitonin gene\u2010related peptide (CGRP) release in the trigeminovascular system. This study aimed to investigate TRPM3 activation and its role in CGRP release, vasodilatory responses, and migraine\u2010relevant behaviors using preclinical models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female Sprague\u2010Dawley rats were used to evaluate CGRP release from trigeminal ganglia (TG) and dura mater following stimulation with the TRPM3 agonist CIM0216. CGRP levels were quantified using ELISA. Myograph studies assessed vasodilation in the middle cerebral artery (MCA) and middle meningeal artery. Immunohistochemistry was used to examine TRPM3 and CGRP localization in TG, dura mater, MCA, and human dura mater. Potential behavioral responses to subcutaneous CIM0216 administration were assessed via mechanical sensitivity tests. Calcium responses to CIM0216 were investigated on CGRP neurons in the TG of transgenic female mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>TRPM3 channel activation with CIM0216 triggered CGRP release from TG at 100 \u03bcM, with indications of enhanced release in female tissues. Immunohistochemistry confirmed colocalization of the TRPM3 channel and CGRP in TG neurons. Additionally, TRPM3 expression was detected in arterial structures, indicating potential involvement in vascular regulation. Although CIM0216 induced CGRP release ex\u00a0vivo, subcutaneous CIM0216 administration was unable to induce allodynia\u2010like symptoms in rats. Application of CIM0216 induced an increase of cytosolic calcium in trigeminal CGRP neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>TRPM3 activation triggers CGRP release and vasodilatation. The findings that TRPM3 induced CGRP release support further investigation of TRPM3 as a therapeutic target for migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.15082","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T09:38:35Z","timestamp":1761298715000},"page":"672-687","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>TRPM3<\/scp>\n                    activation causes\n                    <scp>CGRP<\/scp>\n                    release in trigeminal neurons: Implications for migraine mechanisms"],"prefix":"10.1111","volume":"66","author":[{"given":"Philip V.","family":"Reducha","sequence":"first","affiliation":[{"name":"Sensory Biology Unit, Translational Research Centre Copenhagen University Hospital\u2014Rigshospitalet  Glostrup Denmark"},{"name":"Section of Cell Biology and Physiology, Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas K. 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A.","family":"Edvinsson","sequence":"additional","affiliation":[{"name":"Division of Experimental Vascular Research, Department of Clinical Sciences Lund University  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridoula","family":"Kazantzi","sequence":"additional","affiliation":[{"name":"Sensory Biology Unit, Translational Research Centre Copenhagen University Hospital\u2014Rigshospitalet  Glostrup Denmark"},{"name":"Section of Cell Biology and Physiology, Department of Biology University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia L.","family":"W\u00e6ver","sequence":"additional","affiliation":[{"name":"Sensory Biology Unit, Translational Research Centre Copenhagen University Hospital\u2014Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Lylloff","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology Copenhagen University Hospital\u2014Rigshospitalet  Glostrup Denmark"},{"name":"Brain Water Research, Translational Research Centre Copenhagen University Hospital\u2014Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5066-8306","authenticated-orcid":false,"given":"Connar S. 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