{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:12:03Z","timestamp":1790701923212,"version":"4.1.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T00:00:00Z","timestamp":1697846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Copenhagen University Hospital\u2014Rigshospitalet","award":["E-23831-03"],"award-info":[{"award-number":["E-23831-03"]}]},{"name":"Copenhagen University Hospital\u2014Rigshospitalet","award":["E-23831-01"],"award-info":[{"award-number":["E-23831-01"]}]},{"DOI":"10.13039\/501100009910","name":"Hartmann Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009910","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R373-2021-1199"],"award-info":[{"award-number":["R373-2021-1199"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38), known for its role in migraine pathogenesis, has been identified as a novel drug target. Given the clinical parallels between post-traumatic headache (PTH) and migraine, we explored the possible role of PACAP-38 in the pathogenesis of PTH. To this end, we conducted a randomized, double-blind, placebo-controlled, two-way crossover trial involving adult participants diagnosed with persistent PTH resulting from mild traumatic brain injury.<\/jats:p>\n               <jats:p>Participants were randomly assigned to receive a 20-min continuous intravenous infusion of either PACAP-38 (10\u2005pmol\/kg\/min) or placebo (isotonic saline) on two separate experimental days, with a 1-week washout period in between. The primary outcome was the difference in incidence of migraine-like headache between PACAP-38 and placebo during a 12-h observational period post-infusion. The secondary outcome was the difference in the area under the curve (AUC) for baseline-corrected median headache intensity scores during the same 12-h observational period.<\/jats:p>\n               <jats:p>Of 49 individuals assessed for eligibility, 21 were enrolled and completed the trial. The participants had a mean age of 35.2 years, and 16 (76%) were female. Most [19 of 21 (90%)] had a migraine-like phenotype. During the 12-h observational period, 20 of 21 (95%) participants developed migraine-like headache after intravenous infusion of PACAP-38, compared with two (10%) participants after placebo (P &amp;lt; 0.001). Furthermore, the baseline-corrected AUC values for median headache intensity scores during the 12-h observational period was higher after PACAP-38 than placebo (P &amp;lt; 0.001).<\/jats:p>\n               <jats:p>These compelling results demonstrate that PACAP-38 is potent inducer of migraine-like headache in people with persistent PTH. Thus, targeting PACAP-38 signalling might be a promising avenue for the treatment of PTH.<\/jats:p>","DOI":"10.1093\/brain\/awad367","type":"journal-article","created":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T21:42:54Z","timestamp":1697924574000},"page":"1312-1320","source":"Crossref","is-referenced-by-count":22,"title":["Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial"],"prefix":"10.1093","volume":"147","author":[{"given":"Haidar M","family":"Al-Khazali","sequence":"first","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"},{"name":"Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen 2600 , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rune H","family":"Christensen","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"},{"name":"Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen 2600 , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Dodick","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100 , Denmark"},{"name":"Department of Neurology, Mayo Clinic , Scottsdale, AZ 85259 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basit Ali","family":"Chaudhry","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen 2600 , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faisal Mohammad","family":"Amin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen 2600 , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100 , Denmark"},{"name":"Department of Brain and Spinal Cord Injury, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen 2600 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-8916","authenticated-orcid":false,"given":"Rami","family":"Burstein","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"}],"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":"Harvard Medical School , Boston, MA 02115 , USA"},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center , Boston, MA 02115 , USA"},{"name":"Department of Neurology, Danish Headache Center, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen 2600 , Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen 2100 , Denmark"},{"name":"Department of Brain and Spinal Cord Injury, Copenhagen University Hospital\u2014Rigshospitalet , Copenhagen 2600 , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,21]]},"reference":[{"key":"2024040418391501600_awad367-B1","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S1474-4422(21)00094-6","article-title":"Post-traumatic headache attributed to traumatic brain injury: Classification, clinical characteristics, and treatment","volume":"20","author":"Ashina","year":"2021","journal-title":"Lancet Neurol"},{"key":"2024040418391501600_awad367-B2","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41582-019-0243-8","article-title":"Post-traumatic headache: Epidemiology and pathophysiological insights","volume":"15","author":"Ashina","year":"2019","journal-title":"Nat Rev 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