{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T08:03:16Z","timestamp":1777968196041,"version":"3.51.4"},"reference-count":52,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["19K07849"],"award-info":[{"award-number":["19K07849"]}]},{"name":"JSPS KAKENHI","award":["WS1878886"],"award-info":[{"award-number":["WS1878886"]}]},{"name":"JSPS KAKENHI","award":["2017816"],"award-info":[{"award-number":["2017816"]}]},{"name":"JSPS KAKENHI","award":["CSTB2022NSCQ-MSX1585"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1585"]}]},{"name":"Takeda Science Foundation","award":["19K07849"],"award-info":[{"award-number":["19K07849"]}]},{"name":"Takeda Science Foundation","award":["WS1878886"],"award-info":[{"award-number":["WS1878886"]}]},{"name":"Takeda Science Foundation","award":["2017816"],"award-info":[{"award-number":["2017816"]}]},{"name":"Takeda Science Foundation","award":["CSTB2022NSCQ-MSX1585"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1585"]}]},{"DOI":"10.13039\/100004319","name":"Pfizer Inc.","doi-asserted-by":"publisher","award":["19K07849"],"award-info":[{"award-number":["19K07849"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer Inc.","doi-asserted-by":"publisher","award":["WS1878886"],"award-info":[{"award-number":["WS1878886"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer Inc.","doi-asserted-by":"publisher","award":["2017816"],"award-info":[{"award-number":["2017816"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004319","name":"Pfizer Inc.","doi-asserted-by":"publisher","award":["CSTB2022NSCQ-MSX1585"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1585"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nippon Zoki Pharmaceutical Co., Ltd.","award":["19K07849"],"award-info":[{"award-number":["19K07849"]}]},{"name":"Nippon Zoki Pharmaceutical Co., Ltd.","award":["WS1878886"],"award-info":[{"award-number":["WS1878886"]}]},{"name":"Nippon Zoki Pharmaceutical Co., Ltd.","award":["2017816"],"award-info":[{"award-number":["2017816"]}]},{"name":"Nippon Zoki Pharmaceutical Co., Ltd.","award":["CSTB2022NSCQ-MSX1585"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1585"]}]},{"name":"Kao Corporation","award":["19K07849"],"award-info":[{"award-number":["19K07849"]}]},{"name":"Kao Corporation","award":["WS1878886"],"award-info":[{"award-number":["WS1878886"]}]},{"name":"Kao Corporation","award":["2017816"],"award-info":[{"award-number":["2017816"]}]},{"name":"Kao Corporation","award":["CSTB2022NSCQ-MSX1585"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1585"]}]},{"name":"Japan-China Sasakawa Medical Fellowship","award":["19K07849"],"award-info":[{"award-number":["19K07849"]}]},{"name":"Japan-China Sasakawa Medical Fellowship","award":["WS1878886"],"award-info":[{"award-number":["WS1878886"]}]},{"name":"Japan-China Sasakawa Medical Fellowship","award":["2017816"],"award-info":[{"award-number":["2017816"]}]},{"name":"Japan-China Sasakawa Medical Fellowship","award":["CSTB2022NSCQ-MSX1585"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1585"]}]},{"name":"Chongqing Natural Science Foundation","award":["19K07849"],"award-info":[{"award-number":["19K07849"]}]},{"name":"Chongqing Natural Science Foundation","award":["WS1878886"],"award-info":[{"award-number":["WS1878886"]}]},{"name":"Chongqing Natural Science Foundation","award":["2017816"],"award-info":[{"award-number":["2017816"]}]},{"name":"Chongqing Natural Science Foundation","award":["CSTB2022NSCQ-MSX1585"],"award-info":[{"award-number":["CSTB2022NSCQ-MSX1585"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A migraine is clinically characterized by repeated headache attacks that entail considerable disability. Many patients with migraines experience postdrome, the symptoms of which include tiredness and photophobia. Calcitonin gene-related peptide (GGRP) is critically implicated in migraine pathogenesis. Cortical spreading depolarization (CSD), the biological correlate of migraine aura, sensitizes the trigeminovascular system. In our previous study, CSD caused hypomotility in the light zone and tendency for photophobia at 72 h, at which time trigeminal sensitization had disappeared. We proposed that this CSD-induced disease state would be useful for exploring therapeutic strategies for migraine postdrome. In the present study, we observed that the CGRP receptor antagonist, olcegepant, prevented the hypomotility in the light zone and ameliorated light tolerability at 72 h after CSD induction. Moreover, olcegepant treatment significantly elevated the threshold for facial heat pain at 72 h after CSD. Our results raise the possibility that CGRP blockade may be efficacious in improving hypoactivity in the light environment by enhancing light tolerability during migraine postdrome. Moreover, our data suggest that the CGRP pathway may lower the facial heat pain threshold even in the absence of overt trigeminal sensitization, which provides an important clue to the potential mechanism whereby CGRP blockade confers migraine prophylaxis.<\/jats:p>","DOI":"10.3390\/ijms232213807","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T01:48:08Z","timestamp":1668044888000},"page":"13807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sustained Effects of CGRP Blockade on Cortical Spreading Depolarization-Induced Alterations in Facial Heat Pain Threshold, Light Aversiveness, and Locomotive Activity in the Light Environment"],"prefix":"10.3390","volume":"23","author":[{"given":"Satoshi","family":"Kitagawa","sequence":"first","affiliation":[{"name":"Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhua","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing 400042, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Unekawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yohei","family":"Kayama","sequence":"additional","affiliation":[{"name":"Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoru","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Department of Neurology, Tokyo Dental College Ichikawa General Hospital, Chiba 272-8513, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s10194-020-01208-0","article-title":"Migraine remains second among the world\u2019s causes of disability, and first among young women: Findings from GBD2019","volume":"21","author":"Steiner","year":"2020","journal-title":"J. Headache Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1056\/NEJMra1915327","article-title":"Migraine","volume":"383","author":"Ashina","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s10194-016-0599-8","article-title":"Interictal burden attributable to episodic headache: Findings from the Eurolight project","volume":"17","author":"Lampl","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s40120-021-00305-9","article-title":"Burden of Migraine in Japan: Results of the ObserVational Survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) Study","volume":"11","author":"Matsumori","year":"2022","journal-title":"Neurol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s10194-022-01467-z","article-title":"Measuring interictal burden among people affected by migraine: A descriptive survey study","volume":"23","author":"Hubig","year":"2022","journal-title":"J. Headache Pain"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1212\/WNL.0000000000002789","article-title":"The migraine postdrome: An electronic diary study","volume":"87","author":"Giffin","year":"2016","journal-title":"Neurology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/j.1468-2982.2005.01026.x","article-title":"The postdrome of the acute migraine attack","volume":"26","author":"Kelman","year":"2006","journal-title":"Cephalalgia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s10194-021-01233-7","article-title":"21st century headache: Mapping new territory","volume":"22","author":"Goadsby","year":"2021","journal-title":"J. Headache Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1177\/0271678X16654496","article-title":"Recording, analysis, and interpretation of spreading depolarizations in neurointensive care: Review and recommendations of the COSBID research group","volume":"37","author":"Dreier","year":"2017","journal-title":"J. Cereb Blood Flow Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1002\/ana.410120510","article-title":"Persistent oligemia of rat cerebral cortex in the wake of spreading depression","volume":"12","author":"Lauritzen","year":"1982","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/ana.410280610","article-title":"Timing and topography of cerebral blood flow, aura, and headache during migraine attacks","volume":"28","author":"Olesen","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1002\/ana.410090406","article-title":"Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine","volume":"9","author":"Olesen","year":"1981","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/archneur.56.5.548","article-title":"Functional MRI-BOLD of visually triggered headache in patients with migraine","volume":"56","author":"Cao","year":"1999","journal-title":"Arch. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1001\/archneur.1988.00520260040017","article-title":"Delayed hyperemia following hypoperfusion in classic migraine. Single photon emission computed tomographic demonstration","volume":"45","author":"Andersen","year":"1988","journal-title":"Arch. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/ana.1293","article-title":"Magnetoencephalographic fields from patients with spontaneous and induced migraine aura","volume":"50","author":"Bowyer","year":"2001","journal-title":"Ann. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4687","DOI":"10.1073\/pnas.071582498","article-title":"Mechanisms of migraine aura revealed by functional MRI in human visual cortex","volume":"98","author":"Hadjikhani","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8807","DOI":"10.1523\/JNEUROSCI.0511-10.2010","article-title":"Activation of meningeal nociceptors by cortical spreading depression: Implications for migraine with aura","volume":"30","author":"Zhang","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1002\/ana.22329","article-title":"Activation of central trigeminovascular neurons by cortical spreading depression","volume":"69","author":"Zhang","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1126\/science.1231897","article-title":"Spreading depression triggers headache by activating neuronal Panx1 channels","volume":"339","author":"Karatas","year":"2013","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1177\/0333102412470216","article-title":"Pearls and pitfalls in experimental models of spreading depression","volume":"33","author":"Ayata","year":"2013","journal-title":"Cephalalgia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41582-018-0003-1","article-title":"CGRP as the target of new migraine therapies - successful translation from bench to clinic","volume":"14","author":"Edvinsson","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.6166046","article-title":"Perivascular meningeal projections from cat trigeminal ganglia: Possible pathway for vascular headaches in man","volume":"213","author":"Mayberg","year":"1981","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(19)30185-1","article-title":"Migraine and the trigeminovascular system-40 years and counting","volume":"18","author":"Ashina","year":"2019","journal-title":"Lancet Neurol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/0028-3908(91)90165-8","article-title":"Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion","volume":"30","author":"Buzzi","year":"1991","journal-title":"Neuropharmacology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1139\/y95-143","article-title":"Calcitonin gene related peptide released from dural nerve fibers mediates increase of meningeal blood flow in the rat","volume":"73","author":"Messlinger","year":"1995","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1046\/j.1468-2982.2000.00131.x","article-title":"Release of calcitonin gene-related peptide (CGRP) from guinea pig dura mater in vitro is inhibited by sumatriptan but unaffected by nitric oxide","volume":"20","author":"Eltorp","year":"2000","journal-title":"Cephalalgia"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1046\/j.1468-2982.1994.1405320.x","article-title":"Neuropeptides in migraine and cluster headache","volume":"14","author":"Edvinsson","year":"1994","journal-title":"Cephalalgia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/ana.410280213","article-title":"Vasoactive peptide release in the extracerebral circulation of humans during migraine headache","volume":"28","author":"Goadsby","year":"1990","journal-title":"Ann. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.1002\/art.38656","article-title":"Peripheral calcitonin gene-related peptide receptor activation and mechanical sensitization of the joint in rat models of osteoarthritis pain","volume":"66","author":"Bullock","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1007\/s12576-017-0529-9","article-title":"The potentiating effect of calcitonin gene-related peptide on transient receptor potential vanilloid-1 activity and the electrophysiological responses of rat trigeminal neurons to nociceptive stimuli","volume":"68","author":"Chatchaisak","year":"2018","journal-title":"J. Physiol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.neuroscience.2016.10.013","article-title":"Elevated levels of calcitonin gene-related peptide in upper spinal cord promotes sensitization of primary trigeminal nociceptive neurons","volume":"339","author":"Cornelison","year":"2016","journal-title":"Neuroscience"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1111\/head.13529","article-title":"CGRP and the Trigeminal System in Migraine","volume":"59","author":"Iyengar","year":"2019","journal-title":"Headache"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.jpain.2008.06.011","article-title":"Sensitization of primary afferent nociceptors induced by intradermal capsaicin involves the peripheral release of calcitonin gene-related Peptide driven by dorsal root reflexes","volume":"9","author":"Li","year":"2008","journal-title":"J. Pain"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0304-3959(00)00378-X","article-title":"Arthritic calcitonin\/alpha calcitonin gene-related peptide knockout mice have reduced nociceptive hypersensitivity","volume":"89","author":"Zhang","year":"2001","journal-title":"Pain"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1523\/JNEUROSCI.19-09-03423.1999","article-title":"Regulation of calcitonin gene-related peptide secretion by a serotonergic antimigraine drug","volume":"19","author":"Durham","year":"1999","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0304-3959(00)00475-9","article-title":"An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system","volume":"92","author":"Limmroth","year":"2001","journal-title":"Pain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"11408","DOI":"10.1038\/s41598-020-67948-w","article-title":"Cortical spreading depolarisation-induced facial hyperalgesia, photophobia and hypomotility are ameliorated by sumatriptan and olcegepant","volume":"10","author":"Tang","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.neures.2021.03.010","article-title":"Protracted hypomobility in the absence of trigeminal sensitization after cortical spreading depolarization: Relevance to migraine postdrome","volume":"172","author":"Shibata","year":"2021","journal-title":"Neurosci. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1177\/03331024221083544","article-title":"Atogepant - an orally-administered CGRP antagonist-attenuates activation of meningeal nociceptors by CSD","volume":"42","author":"Strassman","year":"2022","journal-title":"Cephalalgia"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1177\/0333102414550417","article-title":"Low heat pain thresholds in migraineurs between attacks","volume":"35","author":"Schwedt","year":"2015","journal-title":"Cephalalgia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1523\/JNEUROSCI.4496-10.2011","article-title":"Trigeminal nociceptive transmission in migraineurs predicts migraine attacks","volume":"31","author":"Stankewitz","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/brain\/aww097","article-title":"The migraine generator revisited: Continuous scanning of the migraine cycle over 30 days and three spontaneous attacks","volume":"139","author":"Schulte","year":"2016","journal-title":"Brain"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/head.14229","article-title":"Development and validation of a novel patient-reported outcome measure in people with episodic migraine and chronic migraine: The Activity Impairment in Migraine Diary","volume":"62","author":"Lipton","year":"2022","journal-title":"Headache"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neures.2016.06.001","article-title":"Alterations in the threshold of the potassium concentration to evoke cortical spreading depression during the natural estrous cycle in mice","volume":"112","author":"Ebine","year":"2016","journal-title":"Neurosci. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/S1474-4422(16)30293-9","article-title":"Sex differences in the epidemiology, clinical features, and pathophysiology of migraine","volume":"16","author":"Vetvik","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.tins.2020.06.003","article-title":"An Emerging Role for Prolactin in Female-Selective Pain","volume":"43","author":"Chen","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1212\/WNL.0000000000011216","article-title":"Sex Differences in Response to Triptans: A Systematic Review and Meta-analysis","volume":"96","author":"Kurth","year":"2021","journal-title":"Neurology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1468-2982.2004.00726.x","article-title":"Safety, tolerability and pharmacokinetics of BIBN 4096 BS, the first selective small molecule calcitonin gene-related peptide receptor antagonist, following single intravenous administration in healthy volunteers","volume":"24","author":"Iovino","year":"2004","journal-title":"Cephalalgia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1177\/0333102417738249","article-title":"Enhanced susceptibility to cortical spreading depression in two types of Na(+),K(+)-ATPase alpha2 subunit-deficient mice as a model of familial hemiplegic migraine 2","volume":"38","author":"Unekawa","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1177\/0333102417712719","article-title":"Functional interactions between transient receptor potential M8 and transient receptor potential V1 in the trigeminal system: Relevance to migraine pathophysiology","volume":"38","author":"Kayama","year":"2018","journal-title":"Cephalalgia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0091-3057(83)90247-2","article-title":"Further characterization of a simple, automated exploratory model for the anxiolytic effects of benzodiazepines","volume":"18","author":"Blumstein","year":"1983","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/0278-5846(89)90047-X","article-title":"Neuropharmacological and physiological validation of a computer-controlled two-compartment black and white box for the assessment of anxiety","volume":"13","author":"Onaivi","year":"1989","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/13807\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:13:27Z","timestamp":1760145207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/22\/13807"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,9]]},"references-count":52,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232213807"],"URL":"https:\/\/doi.org\/10.3390\/ijms232213807","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,9]]}}}