{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:56:38Z","timestamp":1791327398272,"version":"4.3.1"},"reference-count":244,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"OTKA","doi-asserted-by":"publisher","award":["138125-K"],"award-info":[{"award-number":["138125-K"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003549","name":"OTKA","doi-asserted-by":"publisher","award":["47138-1\/2019-ITM"],"award-info":[{"award-number":["47138-1\/2019-ITM"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"name":"TUDFO","award":["138125-K"],"award-info":[{"award-number":["138125-K"]}]},{"name":"TUDFO","award":["47138-1\/2019-ITM"],"award-info":[{"award-number":["47138-1\/2019-ITM"]}]},{"name":"HUN-REN Hungarian Research Network","award":["138125-K"],"award-info":[{"award-number":["138125-K"]}]},{"name":"HUN-REN Hungarian Research Network","award":["47138-1\/2019-ITM"],"award-info":[{"award-number":["47138-1\/2019-ITM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have a 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors have a 50% responder rate ranging from 56 to 71%. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.<\/jats:p>","DOI":"10.3390\/cells12222649","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T09:10:38Z","timestamp":1700212238000},"page":"2649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4383-4024","authenticated-orcid":false,"given":"Masaru","family":"Tanaka","sequence":"first","affiliation":[{"name":"HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, Tisza Lajos krt. 113, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3435-8866","authenticated-orcid":false,"given":"\u00c1gnes","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"},{"name":"Doctoral School of Clinical Medicine, University of Szeged, Kor\u00e1nyi fasor 6, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8535-5067","authenticated-orcid":false,"given":"Tam\u00e1s","family":"K\u00f6rt\u00e9si","sequence":"additional","affiliation":[{"name":"HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, Tisza Lajos krt. 113, H-6725 Szeged, Hungary"},{"name":"Faculty of Health Sciences and Social Studies, University of Szeged, Temesv\u00e1ri krt. 31, H-6726 Szeged, Hungary"},{"name":"Preventive Health Sciences Research Group, Incubation Competence Centre of the Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6445-8825","authenticated-orcid":false,"given":"D\u00e9lia","family":"Szok","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-3176","authenticated-orcid":false,"given":"J\u00e1nos","family":"Tajti","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-3672","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"HUN-REN-SZTE Neuroscience Research Group, Hungarian Research Network, University of Szeged (HUN-REN-SZTE), Danube Neuroscience Research Laboratory, Tisza Lajos krt. 113, H-6725 Szeged, Hungary"},{"name":"Department of Neurology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis u. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,17]]},"reference":[{"key":"ref_1","unstructured":"(2023, October 12). 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