{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:24:08Z","timestamp":1790861048527,"version":"4.1.0"},"reference-count":63,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["T32AA026577"],"award-info":[{"award-number":["T32AA026577"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["5R01NS130882"],"award-info":[{"award-number":["5R01NS130882"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["UG3DA053094"],"award-info":[{"award-number":["UG3DA053094"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The \u03b4\u2010opioid receptor (\u03b4\u2010receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP\u2010headache model using clinically significant doses of PACAP; determine the effects of \u03b4\u2010receptor activation in this model; and investigate the co\u2010expression of \u03b4\u2010receptors, PACAP and PACAP\u2010PAC1 receptor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>Cephalic allodynia to low doses of acute and chronic PACAP were tested. A triptan (sumatriptan) and a CGRP receptor antagonist (olcegepant) were tested in this model. The \u03b4\u2010receptor agonist SNC80 was tested in PACAP and CGRP\u2010induced headache models. Expression of PACAP, PAC1, CRLR and \u03b4\u2010receptors was determined using in situ hybridisation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>Low doses of PACAP produced dose\u2010dependent acute and chronic cephalic allodynia, blocked by sumatriptan but not by olcegepant. The PAC1 antagonist (M65) did not inhibit CGRP\u2010induced allodynia. There was moderate co\u2010expression of PAC1 and CRLR transcripts in migraine\u2010related regions. SNC80 blocked PACAP\u2010 and CGRP\u2010induced allodynia. There was low co\u2010expression of PACAP and \u03b4\u2010receptors in brain regions measured. However, there was high co\u2010expression of PAC1 and \u03b4\u2010receptors in somatosensory cortex, hippocampus and trigeminal nucleus caudalis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and implications<\/jats:title>\n                    <jats:p>We developed a translationally significant model of PACAP\u2010induced headache, which was mechanistically distinct from CGRP. Activation of \u03b4\u2010receptors blocked PACAP\u2010 and CGRP\u2010induced allodynia, and \u03b4\u2010receptors were highly co\u2010expressed with the PACAP\u2010ergic system. Future studies will examine the functional relationship between \u03b4\u2010receptors and PAC1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.17424","type":"journal-article","created":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T01:35:22Z","timestamp":1736559322000},"page":"1630-1643","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Activation of \u03b4\u2010opioid receptors blocks allodynia in a model of headache induced by PACAP"],"prefix":"10.1111","volume":"182","author":[{"given":"Elizaveta","family":"Mangutov","sequence":"first","affiliation":[{"name":"Center for Clinical Pharmacology, Department of Anesthesiology Washington University School of Medicine  St. Louis Missouri USA"},{"name":"Department of Psychiatry University of Illinois at Chicago  Chicago Illinois 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