{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T02:30:23Z","timestamp":1794018623778,"version":"4.8.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T00:00:00Z","timestamp":1641168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The National Key Research and Development Program of China","award":["2019YFC1709704"],"award-info":[{"award-number":["2019YFC1709704"]}]},{"name":"The Open Research Fund of Chengdu University of Traditional Chinese Medicine Key Laboratory of Systematic Research of Distinctive Chinese Medicine Resources in Southwest China","award":["2020XSGG005"],"award-info":[{"award-number":["2020XSGG005"]}],"id":[{"id":"https:\/\/ror.org\/00pcrz470","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic migraine places a disabling burden on patients, which is extensively modeled by the nitroglycerin (NTG)-treated animal model. Although the NF-\u03baB pathway is involved in an increase in CGRP levels and activation of the trigeminal system in the NTG model, the relationship between NTG and neuroinflammation remains unclear. This study aimed to optimize a chronic NTG rat model with hyperalgesia and the ethological capacity for estimating migraine therapies and to further explore the underlying mechanism of NTG-induced migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Rats were administered different doses of NTG s.c. daily or every 2 d; 30\u2009min and 2\u2009h later, the mechanical threshold was tested. After 9 d, the rats were injected with EB or Cy5.5 for the permeability assay. The other animals were sacrificed, and then, brainstem and caudal trigeminal ganglion were removed to test CGRP, c-Fos and NOS activity; Cytokines levels in the tissue and serum were measured by ELISA; and NF-\u03baB pathway and blood\u2013brain barrier (BBB)-related indicators were analyzed using western blotting. Immunohistochemistry was performed to observe microglial polarization and IL-17A\n                      <jats:sup>+<\/jats:sup>\n                      T cell migration in the medulla oblongata.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NTG (10\u2009mg\/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition, resulting in progressive hyperalgesia and migraine behavior. TNC neuroinflammation with increases in cytokines, CGRP and c-Fos and activation of the NF-\u03baB pathway was observed, and these changes were alleviated by ibuprofen. Furthermore, NTG administration increased BBB permeability by altering the levels functional proteins (RAGE, LRP1, AQP4 and MFSD2A) and structural proteins (ZO-1, Occludin and VE-cadherin-2) to increase peripheral IL-17A permeation into the medulla oblongata, activating microglia and neuroinflammation, and eventually causing hyperalgesia and migraine attack.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study confirmed that NTG (10\u2009mg\/kg, s.c., every 2 d for a total of 5 injections) was the optimal condition to provoke migraine, resulting in mechanical hyperalgesia and observable migraine-like behavior. Furthermore, IL-17A crossed the blood\u2013brain barrier into the medulla oblongata, triggering TNC activation through microglia-mediated neuroinflammation. This process was a novel mechanism in NTG-induced chronic migraine, suggesting that IL-17A might be a novel target in the treatment of migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s10194-021-01374-9","type":"journal-article","created":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T05:05:23Z","timestamp":1641186323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":148,"title":["IL-17 crosses the blood\u2013brain barrier to trigger neuroinflammation: a novel mechanism in nitroglycerin-induced chronic migraine"],"prefix":"10.1186","volume":"23","author":[{"given":"Hao","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqian","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bangyan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tengyun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7454-0873","authenticated-orcid":false,"given":"Shijun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,3]]},"reference":[{"issue":"17","key":"1374_CR1","doi-asserted-by":"publisher","first-page":"e2038","DOI":"10.1212\/wnl.0000000000007371","volume":"92","author":"DS Albrecht","year":"2019","unstructured":"Albrecht DS, Mainero C, Ichijo E, Ward N, Granziera C, Z\u00fcrcher NR, Akeju O, Bonnier G, Price J, Hooker JM, Napadow V, Loggia ML, Hadjikhani N (2019) Imaging of neuroinflammation in migraine with aura: a [(11) C]PBR28 PET\/MRI study. Neurology 92(17):e2038\u2013e2050. https:\/\/doi.org\/10.1212\/wnl.0000000000007371","journal-title":"Neurology"},{"key":"1374_CR2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.jconrel.2018.05.005","volume":"281","author":"S Alli","year":"2018","unstructured":"Alli S, Figueiredo CA, Golbourn B, Sabha N, Wu MY, Bondoc A, Luck A, Coluccia D, Maslink C, Smith C, Wurdak H, Hynynen K, O'Reilly M, Rutka JT (2018) Brainstem blood brain barrier disruption using focused ultrasound: a demonstration of feasibility and enhanced doxorubicin delivery. J Control Release 281:29\u201341. https:\/\/doi.org\/10.1016\/j.jconrel.2018.05.005","journal-title":"J Control Release"},{"issue":"10258","key":"1374_CR3","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/s0140-6736(20)31404-5","volume":"396","author":"Anonymous","year":"2020","unstructured":"Anonymous (2020) Five insights from the global burden of disease study 2019. Lancet 396(10258):1135\u20131159. https:\/\/doi.org\/10.1016\/s0140-6736(20)31404-5","journal-title":"Lancet"},{"issue":"19","key":"1374_CR4","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1056\/NEJMra1915327","volume":"383","author":"M Ashina","year":"2020","unstructured":"Ashina M (2020) Migraine. N Engl J Med 383(19):1866\u20131876. https:\/\/doi.org\/10.1056\/NEJMra1915327","journal-title":"N Engl J Med"},{"issue":"2","key":"1374_CR5","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1111\/j.1468-2982.2009.01864.x","volume":"30","author":"EA Bates","year":"2010","unstructured":"Bates EA, Nikai T, Brennan KC, Fu YH, Charles AC, Basbaum AI, Pt\u00e1\u010dek LJ, Ahn AH (2010) Sumatriptan alleviates nitroglycerin-induced mechanical and thermal allodynia in mice. Cephalalgia 30(2):170\u2013178. https:\/\/doi.org\/10.1111\/j.1468-2982.2009.01864.x","journal-title":"Cephalalgia"},{"issue":"17","key":"1374_CR6","doi-asserted-by":"publisher","first-page":"6619","DOI":"10.1523\/jneurosci.0373-15.2015","volume":"35","author":"R Burstein","year":"2015","unstructured":"Burstein R, Noseda R, Borsook D (2015) Migraine: multiple processes, complex pathophysiology. J Neurosci 35(17):6619\u20136629. https:\/\/doi.org\/10.1523\/jneurosci.0373-15.2015","journal-title":"J Neurosci"},{"issue":"1","key":"1374_CR7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12974-020-01736-1","volume":"17","author":"G Casili","year":"2020","unstructured":"Casili G, Lanza M, Filippone A, Campolo M, Paterniti I, Cuzzocrea S, Esposito E (2020) Dimethyl fumarate alleviates the nitroglycerin (NTG)-induced migraine in mice. J Neuroinflammation 17(1):59. https:\/\/doi.org\/10.1186\/s12974-020-01736-1","journal-title":"J Neuroinflammation"},{"issue":"27","key":"1374_CR8","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.2174\/1381612825666190709204107","volume":"25","author":"C Cavestro","year":"2019","unstructured":"Cavestro C, Ferrero M, Mandrino S, di Tavi M, Rota E (2019) Novelty in inflammation and immunomodulation in migraine. Curr Pharm Des 25(27):2919\u20132936. https:\/\/doi.org\/10.2174\/1381612825666190709204107","journal-title":"Curr Pharm Des"},{"issue":"11","key":"1374_CR9","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.1007\/s00221-020-05923-7","volume":"238","author":"A Cetinkaya","year":"2020","unstructured":"Cetinkaya A, Kilinc E, Camsari C, Ogun MN (2020) Effects of estrogen and progesterone on the neurogenic inflammatory neuropeptides: implications for gender differences in migraine. Exp Brain Res 238(11):2625\u20132639. https:\/\/doi.org\/10.1007\/s00221-020-05923-7","journal-title":"Exp Brain Res"},{"issue":"8","key":"1374_CR10","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1016\/j.pain.2013.03.038","volume":"154","author":"ML Chanda","year":"2013","unstructured":"Chanda ML, Tuttle AH, Baran I, Atlin C, Guindi D, Hathaway G, Israelian N, Levenstadt J, Low D, Macrae L, O\u2019Shea L, Silver A, Zendegui E, Lenselink MA, Spijker S, Ferrari MD, van den Maagdenberg AMJM, Mogil JS (2013) Behavioral evidence for photophobia and stress-related ipsilateral head pain in transgenic Cacna1a mutant mice. Pain 154(8):1254\u20131262. https:\/\/doi.org\/10.1016\/j.pain.2013.03.038","journal-title":"Pain"},{"key":"1374_CR11","doi-asserted-by":"publisher","first-page":"3258572","DOI":"10.1155\/2019\/3258572","volume":"2019","author":"H Chen","year":"2019","unstructured":"Chen H, Pan T, Liu P, Wang P, Xu S (2019) Baihu Jia Guizhi decoction improves rheumatoid arthritis inflammation by regulating succinate\/SUCNR1 metabolic signaling pathway. Evid Based Complement Alternat Med 2019:3258572. https:\/\/doi.org\/10.1155\/2019\/3258572","journal-title":"Evid Based Complement Alternat Med"},{"issue":"6","key":"1374_CR12","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s11916-018-0693-5","volume":"22","author":"TM Chou","year":"2018","unstructured":"Chou TM, Chen SP (2018) Animal models of chronic migraine. Curr Pain Headache Rep 22(6):44. https:\/\/doi.org\/10.1007\/s11916-018-0693-5","journal-title":"Curr Pain Headache Rep"},{"issue":"2","key":"1374_CR13","first-page":"205","volume":"13","author":"V Covelli","year":"1991","unstructured":"Covelli V, Munno I, Pellegrino NM, Altamura M, Decandia P, Marcuccio C, di Venere A, Jirillo E (1991) Are TNF-alpha and IL-1 beta relevant in the pathogenesis of migraine without aura? Acta Neurol (Napoli) 13(2):205\u2013211","journal-title":"Acta Neurol (Napoli)"},{"key":"1374_CR14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.pneurobio.2019.02.002","volume":"177","author":"C Demartini","year":"2019","unstructured":"Demartini C, Greco R, Zanaboni AM, Sances G, de Icco R, Borsook D, Tassorelli C (2019) Nitroglycerin as a comparative experimental model of migraine pain: from animal to human and back. Prog Neurobiol 177:15\u201332. https:\/\/doi.org\/10.1016\/j.pneurobio.2019.02.002","journal-title":"Prog Neurobiol"},{"issue":"1","key":"1374_CR15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1002\/jat.727","volume":"21","author":"KH Diehl","year":"2001","unstructured":"Diehl KH, Hull R, Morton D, Pfister R, Rabemampianina Y, Smith D, Vidal JM, van de Vorstenbosch C, European Federation of Pharmaceutical Industries Association and European Centre for the Validation of Alternative Methods (2001) A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 21(1):15\u201323. https:\/\/doi.org\/10.1002\/jat.727","journal-title":"J Appl Toxicol"},{"issue":"Suppl 1","key":"1374_CR16","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/head.13300","volume":"58","author":"DW Dodick","year":"2018","unstructured":"Dodick DW (2018) A phase-by-phase review of migraine pathophysiology. Headache 58(Suppl 1):4\u201316. https:\/\/doi.org\/10.1111\/head.13300","journal-title":"Headache"},{"issue":"4","key":"1374_CR17","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.autrev.2018.12.004","volume":"18","author":"NP Duarte-Delgado","year":"2019","unstructured":"Duarte-Delgado NP, V\u00e1squez G, Ortiz-Reyes BL (2019) Blood-brain barrier disruption and neuroinflammation as pathophysiological mechanisms of the diffuse manifestations of neuropsychiatric systemic lupus erythematosus. Autoimmun Rev 18(4):426\u2013432. https:\/\/doi.org\/10.1016\/j.autrev.2018.12.004","journal-title":"Autoimmun Rev"},{"issue":"8","key":"1374_CR18","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1038\/s41582-019-0216-y","volume":"15","author":"L Edvinsson","year":"2019","unstructured":"Edvinsson L, Haanes KA, Warfvinge K (2019) Does inflammation have a role in migraine? Nat Rev Neurol 15(8):483\u2013490. https:\/\/doi.org\/10.1038\/s41582-019-0216-y","journal-title":"Nat Rev Neurol"},{"issue":"1","key":"1374_CR19","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/s10194-021-01353-0","volume":"22","author":"\u015eE Erdener","year":"2021","unstructured":"Erdener \u015eE, Kaya Z, Dalkara T (2021) Parenchymal neuroinflammatory signaling and dural neurogenic inflammation in migraine. J Headache Pain 22(1):138. https:\/\/doi.org\/10.1186\/s10194-021-01353-0","journal-title":"J Headache Pain"},{"issue":"2","key":"1374_CR20","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1038\/s41593-017-0059-z","volume":"21","author":"G Faraco","year":"2018","unstructured":"Faraco G, Brea D, Garcia-Bonilla L, Wang G, Racchumi G, Chang H, Buendia I, Santisteban MM, Segarra SG, Koizumi K, Sugiyama Y, Murphy M, Voss H, Anrather J, Iadecola C (2018) Dietary salt promotes neurovascular and cognitive dysfunction through a gut-initiated TH17 response. Nat Neurosci 21(2):240\u2013249. https:\/\/doi.org\/10.1038\/s41593-017-0059-z","journal-title":"Nat Neurosci"},{"issue":"4","key":"1374_CR21","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1080\/1028415x.2019.1627768","volume":"24","author":"M Gautam","year":"2021","unstructured":"Gautam M, Ramanathan M (2021) Ameliorative potential of flavonoids of Aegle marmelos in vincristine-induced neuropathic pain and associated excitotoxicity. Nutr Neurosci 24(4):296\u2013306. https:\/\/doi.org\/10.1080\/1028415x.2019.1627768","journal-title":"Nutr Neurosci"},{"issue":"4","key":"1374_CR22","doi-asserted-by":"publisher","first-page":"2128","DOI":"10.1093\/cercor\/bhz227","volume":"30","author":"J Giesen","year":"2020","unstructured":"Giesen J, F\u00fcchtbauer EM, F\u00fcchtbauer A, Funke K, Koesling D, Russwurm M (2020) AMPA induces NO-dependent cGMP signals in hippocampal and cortical neurons via L-type voltage-gated calcium channels. Cereb Cortex 30(4):2128\u20132143. https:\/\/doi.org\/10.1093\/cercor\/bhz227","journal-title":"Cereb Cortex"},{"issue":"6","key":"1374_CR23","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nri2550","volume":"9","author":"J Goverman","year":"2009","unstructured":"Goverman J (2009) Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 9(6):393\u2013407. https:\/\/doi.org\/10.1038\/nri2550","journal-title":"Nat Rev Immunol"},{"key":"1374_CR24","doi-asserted-by":"publisher","first-page":"105157","DOI":"10.1016\/j.nbd.2020.105157","volume":"147","author":"R Greco","year":"2021","unstructured":"Greco R, Demartini C, Zanaboni A, Casini I, de Icco R, Reggiani A, Misto A, Piomelli D, Tassorelli C (2021) Characterization of the peripheral FAAH inhibitor, URB937, in animal models of acute and chronic migraine. Neurobiol Dis 147:105157. https:\/\/doi.org\/10.1016\/j.nbd.2020.105157","journal-title":"Neurobiol Dis"},{"issue":"1","key":"1374_CR25","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s10194-018-0879-6","volume":"19","author":"R Greco","year":"2018","unstructured":"Greco R, Demartini C, Zanaboni AM, Tassorelli C (2018) Chronic and intermittent administration of systemic nitroglycerin in the rat induces an increase in the gene expression of CGRP in central areas: potential contribution to pain processing. J Headache Pain 19(1):51. https:\/\/doi.org\/10.1186\/s10194-018-0879-6","journal-title":"J Headache Pain"},{"issue":"5","key":"1374_CR26","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1097\/j.pain.0000000000002147","volume":"162","author":"Z Guo","year":"2021","unstructured":"Guo Z, Czerpaniak K, Zhang J, Cao YQ (2021) Increase in trigeminal ganglion neurons that respond to both calcitonin gene-related peptide and pituitary adenylate cyclase-activating polypeptide in mouse models of chronic migraine and posttraumatic headache. Pain 162(5):1483\u20131499. https:\/\/doi.org\/10.1097\/j.pain.0000000000002147","journal-title":"Pain"},{"issue":"3","key":"1374_CR27","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1111\/j.1468-2982.2005.00836.x","volume":"25","author":"G Juhasz","year":"2005","unstructured":"Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolcsanyi J, Bagdy G (2005) Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalalgia 25(3):179\u2013183. https:\/\/doi.org\/10.1111\/j.1468-2982.2005.00836.x","journal-title":"Cephalalgia"},{"key":"1374_CR28","doi-asserted-by":"publisher","unstructured":"Kilinc E, Ankarali S, Torun IE, Dagistan Y (2020) Receptor mechanisms mediating the anti-neuroinflammatory effects of endocannabinoid system modulation in a rat model of migraine. Eur J Neurosci. https:\/\/doi.org\/10.1111\/ejn.14897","DOI":"10.1111\/ejn.14897"},{"issue":"1","key":"1374_CR29","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s10753-019-01115-w","volume":"43","author":"E Kilinc","year":"2020","unstructured":"Kilinc E, Tore F, Dagistan Y, Bugdayci G (2020) Thymoquinone inhibits neurogenic inflammation underlying migraine through modulation of calcitonin gene-related peptide release and stabilization of meningeal mast cells in Glyceryltrinitrate-induced migraine model in rats. Inflammation 43(1):264\u2013273. https:\/\/doi.org\/10.1007\/s10753-019-01115-w","journal-title":"Inflammation"},{"key":"1374_CR30","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2147\/dddt.s117166","volume":"11","author":"L Knapp","year":"2017","unstructured":"Knapp L, Szita B, Kocsis K, V\u00e9csei L, Toldi J (2017) Nitroglycerin enhances the propagation of cortical spreading depression: comparative studies with sumatriptan and novel kynurenic acid analogues. Drug Des Devel Ther 11:27\u201334. https:\/\/doi.org\/10.2147\/dddt.s117166","journal-title":"Drug Des Devel Ther"},{"issue":"3","key":"1374_CR31","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nri.2016.144","volume":"17","author":"T Korn","year":"2017","unstructured":"Korn T, Kallies A (2017) T cell responses in the central nervous system. Nat Rev Immunol 17(3):179\u2013194. https:\/\/doi.org\/10.1038\/nri.2016.144","journal-title":"Nat Rev Immunol"},{"key":"1374_CR32","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3389\/fncel.2019.00136","volume":"13","author":"D Koyuncu Irmak","year":"2019","unstructured":"Koyuncu Irmak D, Kilinc E, Tore F (2019) Shared fate of meningeal mast cells and sensory neurons in migraine. Front Cell Neurosci 13:136. https:\/\/doi.org\/10.3389\/fncel.2019.00136","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"1374_CR33","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s10194-016-0631-z","volume":"17","author":"Y Li","year":"2016","unstructured":"Li Y, Zhang Q, Qi D, Zhang L, Yi L, Li Q, Zhang Z (2016) Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-\u043aB. J Headache Pain 17(1):49. https:\/\/doi.org\/10.1186\/s10194-016-0631-z","journal-title":"J Headache Pain"},{"issue":"13","key":"1374_CR34","doi-asserted-by":"publisher","first-page":"e1365","DOI":"10.1212\/wnl.0000000000009169","volume":"94","author":"RB Lipton","year":"2020","unstructured":"Lipton RB, Goadsby PJ, Smith J, Schaeffler BA, Biondi DM, Hirman J, Pederson S, Allan B, Cady R (2020) Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology 94(13):e1365\u2013e1377. https:\/\/doi.org\/10.1212\/wnl.0000000000009169","journal-title":"Neurology"},{"key":"1374_CR35","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1016\/j.bbi.2019.07.026","volume":"81","author":"Z Liu","year":"2019","unstructured":"Liu Z, Qiu AW, Huang Y, Yang Y, Chen JN, Gu TT, Cao BB, Qiu YH, Peng YP (2019) IL-17A exacerbates neuroinflammation and neurodegeneration by activating microglia in rodent models of Parkinson's disease. Brain Behav Immun 81:630\u2013645. https:\/\/doi.org\/10.1016\/j.bbi.2019.07.026","journal-title":"Brain Behav Immun"},{"issue":"1","key":"1374_CR36","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s10194-019-1070-4","volume":"21","author":"T Long","year":"2020","unstructured":"Long T, He W, Pan Q, Zhang S, Zhang D, Qin G, Chen L, Zhou J (2020) Microglia P2X4R-BDNF signalling contributes to central sensitization in a recurrent nitroglycerin-induced chronic migraine model. J Headache Pain 21(1):4. https:\/\/doi.org\/10.1186\/s10194-019-1070-4","journal-title":"J Headache Pain"},{"issue":"4","key":"1374_CR37","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/j.immuni.2019.03.021","volume":"50","author":"MJ Mcgeachy","year":"2019","unstructured":"Mcgeachy MJ, Cua DJ, Gaffen SL (2019) The IL-17 family of cytokines in health and disease. Immunity 50(4):892\u2013906. https:\/\/doi.org\/10.1016\/j.immuni.2019.03.021","journal-title":"Immunity"},{"issue":"5","key":"1374_CR38","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41593-019-0369-4","volume":"22","author":"J Niu","year":"2019","unstructured":"Niu J, Tsai HH, Hoi KK, Huang N, Yu G, Kim K, Baranzini SE, Xiao L, Chan JR, Fancy SPJ (2019) Aberrant oligodendroglial-vascular interactions disrupt the blood-brain barrier, triggering CNS inflammation. Nat Neurosci 22(5):709\u2013718. https:\/\/doi.org\/10.1038\/s41593-019-0369-4","journal-title":"Nat Neurosci"},{"issue":"8","key":"1374_CR39","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.euroneuro.2015.04.001","volume":"25","author":"C Nozaki","year":"2015","unstructured":"Nozaki C, Markert A, Zimmer A (2015) Inhibition of FAAH reduces nitroglycerin-induced migraine-like pain and trigeminal neuronal hyperactivity in mice. Eur Neuropsychopharmacol 25(8):1388\u20131396. https:\/\/doi.org\/10.1016\/j.euroneuro.2015.04.001","journal-title":"Eur Neuropsychopharmacol"},{"issue":"2","key":"1374_CR40","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/j.pain.2013.10.004","volume":"155","author":"AA Pradhan","year":"2014","unstructured":"Pradhan AA, Smith ML, Mcguire B et al (2014) Characterization of a novel model of chronic migraine. Pain 155(2):269\u2013274. https:\/\/doi.org\/10.1016\/j.pain.2013.10.004","journal-title":"Pain"},{"issue":"2","key":"1374_CR41","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1111\/j.1468-2982.2004.00639.x","volume":"24","author":"G Sances","year":"2004","unstructured":"Sances G, Tassorelli C, Pucci E, Ghiotto N, Sandrini G, Nappi G (2004) Reliability of the nitroglycerin provocative test in the diagnosis of neurovascular headaches. Cephalalgia 24(2):110\u2013119. https:\/\/doi.org\/10.1111\/j.1468-2982.2004.00639.x","journal-title":"Cephalalgia"},{"issue":"21","key":"1374_CR42","doi-asserted-by":"publisher","first-page":"2011","DOI":"10.1212\/wnl.0000000000003963","volume":"88","author":"LH Schulte","year":"2017","unstructured":"Schulte LH, Allers A, May A (2017) Hypothalamus as a mediator of chronic migraine: evidence from high-resolution fMRI. Neurology 88(21):2011\u20132016. https:\/\/doi.org\/10.1212\/wnl.0000000000003963","journal-title":"Neurology"},{"issue":"7","key":"1374_CR43","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1093\/brain\/aww097","volume":"139","author":"LH Schulte","year":"2016","unstructured":"Schulte LH, May A (2016) The migraine generator revisited: continuous scanning of the migraine cycle over 30 days and three spontaneous attacks. Brain 139(7):1987\u20131993. https:\/\/doi.org\/10.1093\/brain\/aww097","journal-title":"Brain"},{"issue":"1","key":"1374_CR44","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s10194-016-0624-y","volume":"17","author":"KJ Sufka","year":"2016","unstructured":"Sufka KJ, Staszko SM, Johnson AP, Davis ME, Davis RE, Smitherman TA (2016) Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats. J Headache Pain 17(1):40. https:\/\/doi.org\/10.1186\/s10194-016-0624-y","journal-title":"J Headache Pain"},{"issue":"1","key":"1374_CR45","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/jnr.24331","volume":"98","author":"S Sulhan","year":"2020","unstructured":"Sulhan S, Lyon KA, Shapiro LA, Huang JH (2020) Neuroinflammation and blood-brain barrier disruption following traumatic brain injury: pathophysiology and potential therapeutic targets. J Neurosci Res 98(1):19\u201328. https:\/\/doi.org\/10.1002\/jnr.24331","journal-title":"J Neurosci Res"},{"key":"1374_CR46","doi-asserted-by":"publisher","unstructured":"Tardiolo G, Bramanti P, Mazzon E (2019) Migraine: experimental models and novel therapeutic approaches. Int J Mol Sci 20(12). https:\/\/doi.org\/10.3390\/ijms20122932","DOI":"10.3390\/ijms20122932"},{"key":"1374_CR47","doi-asserted-by":"publisher","unstructured":"Tasleem F, Azhar I, Ali SN et al (2014) Analgesic and anti-inflammatory activities of Piper nigrum L. Asian Pac J trop med 7s1:S461-468. https:\/\/doi.org\/10.1016\/s1995-7645(14)60275-3","DOI":"10.1016\/s1995-7645(14)60275-3"},{"key":"1374_CR48","doi-asserted-by":"publisher","unstructured":"Turksen K (2011) Permeability barrier. Humana Press. https:\/\/doi.org\/10.1007\/978-1-61779-191-8","DOI":"10.1007\/978-1-61779-191-8"},{"key":"1374_CR49","doi-asserted-by":"publisher","first-page":"105080","DOI":"10.1016\/j.nbd.2020.105080","volume":"145","author":"EA Van Vliet","year":"2020","unstructured":"Van Vliet EA, Ndode-Ekane XE, Lehto LJ et al (2020) Long-lasting blood-brain barrier dysfunction and neuroinflammation after traumatic brain injury. Neurobiol Dis 145:105080. https:\/\/doi.org\/10.1016\/j.nbd.2020.105080","journal-title":"Neurobiol Dis"},{"key":"1374_CR50","doi-asserted-by":"publisher","first-page":"9547056","DOI":"10.1155\/2017\/9547056","volume":"2017","author":"V Vellani","year":"2017","unstructured":"Vellani V, Moschetti G, Franchi S, Giacomoni C, Sacerdote P, Amodeo G (2017) Effects of NSAIDs on the release of calcitonin gene-related peptide and prostaglandin E (2) from rat trigeminal ganglia. Mediat Inflamm 2017:9547056. https:\/\/doi.org\/10.1155\/2017\/9547056","journal-title":"Mediat Inflamm"},{"issue":"5","key":"1374_CR51","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s00401-015-1402-7","volume":"129","author":"A Waisman","year":"2015","unstructured":"Waisman A, Hauptmann J, Regen T (2015) The role of IL-17 in CNS diseases. Acta Neuropathol 129(5):625\u2013637. https:\/\/doi.org\/10.1007\/s00401-015-1402-7","journal-title":"Acta Neuropathol"},{"issue":"3","key":"1374_CR52","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1177\/0333102417728873","volume":"39","author":"K Warfvinge","year":"2019","unstructured":"Warfvinge K, Edvinsson L (2019) Distribution of CGRP and CGRP receptor components in the rat brain. Cephalalgia 39(3):342\u2013353. https:\/\/doi.org\/10.1177\/0333102417728873","journal-title":"Cephalalgia"},{"issue":"1","key":"1374_CR53","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3892\/etm.2019.8201","volume":"19","author":"W Wen","year":"2020","unstructured":"Wen W, Chen H, Fu K, Wei J, Qin L, Pan T, Xu S (2020) Fructus Viticis methanolic extract attenuates trigeminal hyperalgesia in migraine by regulating injury signal transmission. Exp Ther Med 19(1):85\u201394. https:\/\/doi.org\/10.3892\/etm.2019.8201","journal-title":"Exp Ther Med"},{"key":"1374_CR54","doi-asserted-by":"publisher","unstructured":"Yao G, Man YH, Li AR et al. (2020) NO up-regulates migraine-related CGRP via activation of an Akt\/GSK-3\u03b2\/NF-\u03baB signaling cascade in trigeminal ganglion neurons. Aging 12:6370-6384. https:\/\/doi.org\/10.18632\/aging.103031","DOI":"10.18632\/aging.103031"},{"issue":"1","key":"1374_CR55","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12974-019-1673-3","volume":"17","author":"S Zhang","year":"2020","unstructured":"Zhang S, Hu L, Jiang J, Li H, Wu Q, Ooi K, Wang J, Feng Y, Zhu D, Xia C (2020) HMGB1\/RAGE axis mediates stress-induced RVLM neuroinflammation in mice via impairing mitophagy flux in microglia. J Neuroinflammation 17(1):15. https:\/\/doi.org\/10.1186\/s12974-019-1673-3","journal-title":"J Neuroinflammation"}],"container-title":["The Journal of Headache and Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-021-01374-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s10194-021-01374-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s10194-021-01374-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,3]],"date-time":"2022-01-03T05:05:34Z","timestamp":1641186334000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejournalofheadacheandpain.biomedcentral.com\/articles\/10.1186\/s10194-021-01374-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,3]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1374"],"URL":"https:\/\/doi.org\/10.1186\/s10194-021-01374-9","relation":{},"ISSN":["1129-2369","1129-2377"],"issn-type":[{"value":"1129-2369","type":"print"},{"value":"1129-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,3]]},"assertion":[{"value":"29 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The IRB of the Institute of Materia Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine have approved this study. All participants have provided written informed consent to participate.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no conflict of interest exits regarding the contents of the manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1"}}