{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:40:20Z","timestamp":1792726820535,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Enhancement of endogenous opioid signaling through inhibition of enkephalin degradation has emerged as a potential strategy for pain control, yet its role in migraine remains unclear. This study investigated whether spinorphin, an endogenous inhibitor of multiple enkephalinases, attenuates trigeminovascular activation and migraine\u2010like responses in experimental migraine. Migraine\u2010like pain was induced in male Wistar rats by nitroglycerin. The effects of spinorphin were evaluated using periorbital and plantar von Frey tests, followed by assessment of c\u2010Fos levels in the trigeminal nucleus caudalis (TNC), calcitonin gene\u2010related peptide (CGRP) levels in the trigeminal ganglion (TG) and TNC, and meningeal mast cell degranulation. Opioid receptor involvement was examined using nalmefene. In complementary ex\u00a0vivo hemiskull preparations, capsaicin\u2010evoked CGRP release was quantified, and the interaction between spinorphin and sumatriptan was investigated. Spinorphin dose\u2010dependently alleviated cephalic and extracephalic mechanical hypersensitivity, reduced c\u2010Fos levels, decreased CGRP concentrations in the TG and TNC, and inhibited meningeal mast cell degranulation. These protective effects were markedly attenuated by nalmefene, supporting the involvement of opioid receptor\u2010mediated mechanisms. In ex\u00a0vivo preparations, spinorphin selectively reduced capsaicin\u2010induced CGRP levels in the superfusates without affecting basal CGRP levels, and this effect was abolished by nalmefene. Moreover, spinorphin enhanced the inhibitory effect of sumatriptan on capsaicin\u2010stimulated CGRP levels. Spinorphin attenuates behavioral, neurochemical, and neuroinflammatory features of experimental migraine, at least partly through mechanisms involving endogenous opioid signaling. These findings suggest enkephalinase inhibition as a promising therapeutic approach for migraine and support further investigation of spinorphin as a potential adjunct to established antimigraine therapies.<\/jats:p>","DOI":"10.1111\/ejn.70728","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:22:01Z","timestamp":1792725721000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spinorphin Ameliorates Nitroglycerin\u2010Induced Migraine\u2010Like Responses and Trigeminovascular Neuroinflammation Potentially Through Opioid Receptor\u2010Mediated Mechanisms"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8140-9892","authenticated-orcid":false,"given":"Cemalettin","family":"Demir","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Bolu Abant Izzet Baysal University  Bolu 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