{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:24:36Z","timestamp":1790861076463,"version":"4.1.0"},"reference-count":163,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Migraine is a complex and disabling neurological disorder. Recent years have witnessed the development and emergence of novel treatments for the condition, namely those targeting calcitonin gene\u2010related peptide (CGRP). However, there remains a substantial need for further treatments for those unresponsive to current therapies. Targeting pituitary adenylate cyclase\u2010activating polypeptide (PACAP) as a possible therapeutic strategy in the primary headache disorders has gained interest over recent years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This review will summarize what we know about PACAP to date: its expression, receptors, roles in migraine and cluster headache biology, insights gained from preclinical and clinical models of migraine, and therapeutic scope.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PACAP shares homology with vasoactive intestinal polypeptide (VIP) and is one of several vasoactive neuropeptides along with CGRP and VIP, which has been implicated in migraine neurobiology. PACAP is widely expressed in areas of interest in migraine pathophysiology, such as the thalamus, trigeminal nucleus caudalis, and sphenopalatine ganglion. Preclinical evidence suggests a role for PACAP in trigeminovascular sensitization, while clinical evidence shows ictal release of PACAP in migraine and intravenous infusion of PACAP triggering attacks in susceptible individuals. PACAP leads to dural vasodilatation and secondary central phenomena via its binding to different G\u2010protein\u2010coupled receptors, and intracellular downstream effects through cyclic adenosine monophosphate (cAMP) and phosphokinase C (PKC). Targeting PACAP as a therapeutic strategy in headache has been explored using monoclonal antibodies developed against PACAP and against the PAC1 receptor, with initial positive results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Future clinical trials hold considerable promise for a new therapeutic approach using PACAP\u2010targeted therapies in both migraine and cluster headache.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.52119","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T05:11:37Z","timestamp":1718687497000},"page":"1654-1668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Pituitary adenylate cyclase\u2010activating polypeptide targeted treatments in primary headache disorders"],"prefix":"10.1002","volume":"11","author":[{"given":"Nazia","family":"Karsan","sequence":"first","affiliation":[{"name":"Headache Group, The Wolfson Sensory, Pain and Regeneration Centre (SPaRC), NIHR King's Clinical Research Facility and SLaM Biomedical Research Centre Institute of Psychiatry, Psychology and Neuroscience, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Edvinsson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Institute of Clinical Sciences Lund University  221 84 Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo","family":"Vecsei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Albert Szent\u2010Gy\u00f6rgyi Medical School, and HUN\u2010REN\u2010SZTE Neuroscience Research Group, Hungarian Research Network University of Szeged  Semmelweis u. 6 Szeged H\u20106725 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