{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:42:39Z","timestamp":1786628559006,"version":"build-2736575974"},"reference-count":43,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R310-2018-3711"],"award-info":[{"award-number":["R310-2018-3711"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R403-2022-1352"],"award-info":[{"award-number":["R403-2022-1352"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001732","name":"Danmarks Grundforskningsfond","doi-asserted-by":"publisher","award":["DNRF188"],"award-info":[{"award-number":["DNRF188"]}],"id":[{"id":"10.13039\/501100001732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To examine whether plasma or serum pituitary adenylate cyclase-activating polypeptide (PACAP) levels differ between people with migraine and healthy controls (HCs), and to assess evidence for dynamic alterations during migraine attacks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature search was conducted in PubMed and Embase from inception to December 19, 2025. Eligible studies measured PACAP in plasma or serum of adult or pediatric participants with migraine and reported comparisons with HCs, and\/or between ictal and interictal phases. Two reviewers independently screened articles, extracted data, and assessed risk of bias using the QUADAS-2 tool.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eleven studies met the inclusion criteria, comprising seven adult and four pediatric studies. Findings were inconsistent across studies, with some reporting higher PACAP-38 levels in participants with migraine, while others found no differences or even lower levels compared with HCs. Five studies compared ictal and interictal levels, but results were incongruent and lacked intraindividual measurements. Furthermore, all studies were judged to be at high overall risk of bias, primarily due to limitations in participant selection and index test methodology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Current evidence on plasma or serum PACAP-38 levels in migraine is limited and inconsistent. The lack of intraindividual ictal-interictal comparisons and variability in study design and assays further weaken conclusions. Standardized, high-quality studies are essential to resolve existing uncertainties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>The study protocol was prospectively registered in PROSPERO (CRD42024601373).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024261468031","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T14:08:35Z","timestamp":1786457315000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Blood levels of PACAP in migraine: A systematic review"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9682-7796","authenticated-orcid":false,"given":"Pil L.","family":"J\u00f8rgensen","sequence":"first","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5375-7350","authenticated-orcid":false,"given":"Sarra","family":"Al-Khazali","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3384-3579","authenticated-orcid":false,"given":"Rune H\u00e4ckert","family":"Christensen","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Translational Research Center, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-3369","authenticated-orcid":false,"given":"Haidar M.","family":"Al-Khazali","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Translational Research Center, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0951-5804","authenticated-orcid":false,"given":"Messoud","family":"Ashina","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6268-727X","authenticated-orcid":false,"given":"H\u00e5kan","family":"Ashina","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"},{"name":"Translational Research Center, Copenhagen University Hospital \u2013 Rigshospitalet, Copenhagen, Denmark"},{"name":"Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1915327"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30185-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaf284"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420929026"},{"key":"e_1_3_3_6_2","first-page":"333102425136424","article-title":"PACAP Versus CGRP in migraine: from mouse models to clinical translation","volume":"45","author":"Pietra AD","year":"2025","unstructured":"Pietra AD, Kuburas A, Russo AF. PACAP Versus CGRP in migraine: from mouse models to clinical translation. Cephalalgia 2025; 45: 3331024251364242.","journal-title":"Cephalalgia"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14053"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn307"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-024-01011-4"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2314577"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.12949"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2015.08.017"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05781-0"},{"key":"e_1_3_3_14_2","first-page":"097275312513401","article-title":"Comparative analysis of CGRP, VIP and PACAP-38 levels in migraine with and without aura: a case-control study","volume":"31","author":"Sreevani N","year":"2025","unstructured":"Sreevani N, Ramesh B, Maheshkumar K, et al. Comparative analysis of CGRP, VIP and PACAP-38 levels in migraine with and without aura: a case-control study. 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Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 2020; 368: l6890.","journal-title":"BMJ"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aet293"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2008.01.022"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-155-8-201110180-00009"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-016-0660-7"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102420970889"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1177\/03331024251363560"},{"key":"e_1_3_3_33_2","unstructured":"Lundbeck A\/S H. Lundbeck announces positive phase IIb top-line results with bocunebart (Lu AG09222; anti-PACAP mAb) in migraine prevention https:\/\/news.cision.com\/h\u2013lundbeck-a-s\/r\/lundbeck-announces-positive-phase-iib-top-line-results-with-bocunebart\u2013lu-ag09222\u2013anti-pacap-mab\u2013 c4307114 (2026 accessed 13 April 2026)."},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/03331024251368757"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14711"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.001370"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.15011"},{"key":"e_1_3_3_38_2","article-title":"Elucidating the nociceptive role of CGRP in migraine headache","volume":"8","author":"Melo-Carrillo A","year":"2026","unstructured":"Melo-Carrillo A, Strassman A, Burstein R. Elucidating the nociceptive role of CGRP in migraine headache. 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