{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T04:26:54Z","timestamp":1786854414992,"version":"build-2736575974"},"reference-count":210,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Wroclaw Medical University","doi-asserted-by":"crossref","award":["SUBZ.A520.26.030"],"award-info":[{"award-number":["SUBZ.A520.26.030"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"crossref"}]},{"award":["SUBZ.A520.26.030"],"award-info":[{"award-number":["SUBZ.A520.26.030"]}],"id":[{"id":"https:\/\/ror.org\/01qpw1b93","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Beyond the well-established roles of serotonin and calcitonin gene-related peptide (CGRP), the contribution of dopamine (DA) to migraine pathophysiology remains a subject of intense investigation. DA acts as a neuromodulator, functioning both as a homeostatic pain filter and a driver of premonitory and autonomic symptoms. This review provides a comprehensive synthesis of DA\u2019s involvement in migraine, proposing an integrated model that spans from molecular signaling to a systemic phenotype. A comprehensive search of the PubMed database (1976\u20132026) was performed. The analysis evaluates data across receptor signaling, hypothalamic connectivity (specifically the A11 nucleus), genetic susceptibility markers and advanced neuroimaging studies. Current evidence identifies dopamine as a gatekeeper of the trigeminovascular threshold, with the hypothalamic A11 nucleus serving as a modulatory hub. Within this circuit, DA exerts concentration-dependent effects: high-affinity D2 receptor activation promotes antinociception, whereas low-affinity D1-like receptors facilitate nociceptive signaling. Clinically, this manifests as a \u201cdopaminergic phenotype\u201d characterized by yawning, nausea, and reward-system dysfunction. This phenotype extends beyond migraine, showing links to comorbidities such as restless legs syndrome (RLS) and attention-deficit\/hyperactivity disorder (ADHD). DA\u2019s role in migraine is state-dependent and interconnected with CGRP and serotonergic pathways. Recognizing the dopaminergic phenotype is essential for capturing the clinical heterogeneity of the disorder and may pave the way for personalized, mechanism-based therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms27167262","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T10:39:01Z","timestamp":1786703941000},"page":"7262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dopaminergic Dysregulation in Migraine: From Hypothalamic A11 Dysfunction to a Systemic Biobehavioral Phenotype"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7202-5420","authenticated-orcid":false,"given":"Jakub","family":"Przegra\u0142ek","sequence":"first","affiliation":[{"name":"Department of Neurology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0085-2919","authenticated-orcid":false,"given":"Filip","family":"Targosi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9093-180X","authenticated-orcid":false,"given":"Karol","family":"Marschollek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2458-5755","authenticated-orcid":false,"given":"Izabela","family":"\u0141aczma\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-5039","authenticated-orcid":false,"given":"Lanfranco","family":"Pellesi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u0142awomir","family":"Budrewicz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3173-8337","authenticated-orcid":false,"given":"Marta","family":"Nowakowska-Kotas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-2803","authenticated-orcid":false,"given":"Marta","family":"Waliszewska-Pros\u00f3\u0142","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1124\/pharmrev.122.000618","article-title":"Dopamine, Immunity, and Disease","volume":"75","author":"Channer","year":"2023","journal-title":"Pharmacol. 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