{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:59:36Z","timestamp":1780505976218,"version":"3.54.1"},"reference-count":41,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100013826","name":"Candys Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013826","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"}]},{"name":"Lundbeck Foundation Scholarship"},{"name":"Lundbeck Foundation Professor Grant","award":["R310-2018\u20133711"],"award-info":[{"award-number":["R310-2018\u20133711"]}]},{"name":"Foreningen til st\u00f8tte af forskning ved Dansk Hovedpine Center"},{"name":"BRIDGE \u2013 Translational Excellence Programme, Faculty of Health and Medical Sciences, University of Copenhagen, supported by the Novo Nordisk Foundation","award":["NNF23SA0087869"],"award-info":[{"award-number":["NNF23SA0087869"]}]},{"name":"Rigshospitalets Forskningspuljer","award":["E-23327-03"],"award-info":[{"award-number":["E-23327-03"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate whether blockade of hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels modifies migraine induced by activation of vascular ATP-sensitive potassium (K\n                      <jats:sub>ATP<\/jats:sub>\n                      ) channels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single-centre, randomised, double-blind, placebo-controlled, two-way crossover study in adults with migraine without aura. On two separate days, participants received intravenous levcromakalim followed immediately by either oral ivabradine or placebo in a balanced order. The primary endpoint was the 12-h incidence of levcromakalim-induced migraine. Secondary endpoints included the area under the curve (AUC) for headache intensity and haemodynamic responses. Parallel preclinical experiments were performed in a validated mouse model using von Frey-based tactile sensitivity to assess whether ivabradine, given as pretreatment or as rescue medication, alters levcromakalim-induced hypersensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty seven of 31 individuals completed the human study and provided data for the final analysis. Ivabradine did not modify the incidence of levcromakalim-induced migraine (22 of 27 after ivabradine and 22 of 27 after placebo;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009&gt;\u20090.99) or the AUC for headache intensity (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2009=\u20090.11). Haemodynamic responses did not differ between study days. In mice, ivabradine at multiple doses neither prevented nor reversed tactile hypersensitivity induced by repeated levcromakalim administration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      HCN channel blockade does not influence migraine or nociceptive behaviour provoked by vascular K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel activation. These convergent human and preclinical findings indicate that HCN channels are not essential for the downstream transformation of vascular K\n                      <jats:sub>ATP<\/jats:sub>\n                      channel activation into migraine pain and support a model in which migraine initiation arises from signalling at the vessel-to-neuron interface.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov; NCT04853797; Registered: 16-03-2021. Preclinical experiments were not preregistered beyond the animal ethical license (2017-15-0201-01358) from the Danish Animal Experiments Inspectorate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024261431770","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T09:51:12Z","timestamp":1775209872000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Migraine induced by vascular K\n                    <sub>ATP<\/sub>\n                    channel activation is independent of HCN channel activity: A randomised controlled trial with translational validation"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0041-7389","authenticated-orcid":false,"given":"Zixuan Alice","family":"Zhuang","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\/0000-0002-7166-0976","authenticated-orcid":false,"given":"Janu","family":"Thuraiaiyah","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9136-1367","authenticated-orcid":false,"given":"Lili","family":"Kokoti","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2788-8743","authenticated-orcid":false,"given":"Rogelio Dominguez","family":"Moreno","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":"Department of Neurology and Psychiatry, Difficult-to-Treat Headache Clinic, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9702-1451","authenticated-orcid":false,"given":"Emil","family":"Gozalov","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\/0000-0002-3046-9753","authenticated-orcid":false,"given":"Zahra","family":"Hakimzadeh","sequence":"additional","affiliation":[{"name":"Copenhagen University Hospital \u2013 Rigshospitalet"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, 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