{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:18:00Z","timestamp":1785734280063,"version":"3.56.0"},"reference-count":121,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T00:00:00Z","timestamp":1721260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Ministry of Science and Higher Education","doi-asserted-by":"publisher","award":["PMMH-RI number 2023.2\/5\/5-GW"],"award-info":[{"award-number":["PMMH-RI number 2023.2\/5\/5-GW"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Although the introduction of drugs targeting calcitonin gene-related peptide (CGRP) revolutionized migraine treatment, still a substantial proportion of migraine patients do not respond satisfactorily to such a treatment, and new therapeutic targets are needed. Therefore, molecular studies on migraine pathogenesis are justified. Oxidative stress is implicated in migraine pathogenesis, as many migraine triggers are related to the production of reactive oxygen and nitrogen species (RONS). Migraine has been proposed as a superior mechanism of the brain to face oxidative stress resulting from energetic imbalance. However, the precise mechanism behind the link between migraine and oxidative stress is not known. Nociceptive primary afferent nerve fiber endings express ion channel receptors that change harmful stimuli into electric pain signals. Transient receptor potential cation channel subfamily A member 1 (TRPA1) is an ion channel that can be activated by oxidative stress products and stimulate the release of CGRP from nerve endings. It is a transmembrane protein with ankyrin repeats and conserved cysteines in its N-terminus embedded in the cytosol. TRPA1 may be a central element of the signaling pathway from oxidative stress and NO production to CGRP release, which may play a critical role in headache induction. In this narrative review, we present information on the role of oxidative stress in migraine pathogenesis and provide arguments that TRPA1 may be \u201ca missing link\u201d between oxidative stress and migraine and therefore a druggable target in this disease.<\/jats:p>","DOI":"10.3390\/molecules29143385","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T16:51:12Z","timestamp":1721321472000},"page":"3385","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The TRPA1 Ion Channel Mediates Oxidative Stress-Related Migraine Pathogenesis"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0748-7080","authenticated-orcid":false,"given":"Michal","family":"Fila","sequence":"first","affiliation":[{"name":"Department of Developmental Neurology and Epileptology, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-4103","authenticated-orcid":false,"given":"Lukasz","family":"Przyslo","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology and Epileptology, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7203-271X","authenticated-orcid":false,"given":"Marcin","family":"Derwich","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Medical University of Lodz, 92-217 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Sobczuk","sequence":"additional","affiliation":[{"name":"Emergency Medicine and Disaster Medicine Department, Medical University of Lodz, 92-209 Lodz, Poland"},{"name":"Department of Orthopaedics and Traumatology, Polish Mothers\u2019 Memorial Hospital\u2013Research Institute, Rzgowska 281, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5373-4783","authenticated-orcid":false,"given":"Elzbieta","family":"Pawlowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, Medical University of Lodz, 92-217 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9539-9584","authenticated-orcid":false,"given":"Janusz","family":"Blasiak","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Collegium Medicum, Mazovian Academy in Plock, 09-402 Plock, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12325-023-02650-7","article-title":"Unmet Needs in the Acute Treatment of Migraine","volume":"41","author":"Bentivegna","year":"2024","journal-title":"Adv. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1111\/bcp.12618","article-title":"CGRP receptor antagonists and antibodies against CGRP and its receptor in migraine treatment","volume":"80","author":"Edvinsson","year":"2015","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s10194-019-1043-7","article-title":"Animal models of migraine and experimental techniques used to examine trigeminal sensory processing","volume":"20","author":"Harriott","year":"2019","journal-title":"J. Headache Pain"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14449","DOI":"10.1038\/s41598-023-41521-7","article-title":"Deciphering migraine pain mechanisms through electrophysiological insights of trigeminal ganglion neurons","volume":"13","author":"Vongseenin","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1152\/physrev.00034.2015","article-title":"Pathophysiology of Migraine: A Disorder of Sensory Processing","volume":"97","author":"Goadsby","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_6","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_7","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_8","unstructured":"Schmidt, R.F., and Willis, W.D. (2007). Transduction and Encoding of Noxious Stimuli. Encyclopedia of Pain, Springer."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1080\/17512433.2016.1183481","article-title":"Pain transduction: A pharmacologic perspective","volume":"9","author":"McEntire","year":"2016","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Koivisto, A., Jalava, N., Bratty, R., and Pertovaara, A. (2018). TRPA1 Antagonists for Pain Relief. Pharmaceuticals, 11.","DOI":"10.3390\/ph11040117"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41392-023-01464-x","article-title":"TRP (transient receptor potential) ion channel family: Structures, biological functions and therapeutic interventions for diseases","volume":"8","author":"Zhang","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"136380","DOI":"10.1016\/j.neulet.2021.136380","article-title":"The role of TRP ion channels in migraine and headache","volume":"768","author":"Iannone","year":"2022","journal-title":"Neurosci. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"141","DOI":"10.31083\/j.jin2105141","article-title":"Chronic Migraine: A Narrative Review on the Use of Botulinum Toxin with Clinical Indications and Future Directions","volume":"21","author":"Raciti","year":"2022","journal-title":"J. Integr. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s12264-020-00569-5","article-title":"Implications of Transient Receptor Potential Cation Channels in Migraine Pathophysiology","volume":"37","author":"Shibata","year":"2021","journal-title":"Neurosci. Bull."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1096\/fasebj.2020.34.s1.02286","article-title":"Channelopathy and Carbohydrates: Bad Mix for Migraines","volume":"34","author":"Stanton","year":"2020","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41573-021-00268-4","article-title":"Advances in TRP channel drug discovery: From target validation to clinical studies","volume":"21","author":"Koivisto","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1113\/jphysiol.2003.050633","article-title":"Capsaicin-sensitive neurogenic sensory vasodilatation in the dura mater of the rat","volume":"552","author":"Dux","year":"2003","journal-title":"J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1111\/j.1460-9568.2009.06702.x","article-title":"TRPA1-mediated responses in trigeminal sensory neurons: Interaction between TRPA1 and TRPV1","volume":"29","author":"Salas","year":"2009","journal-title":"Eur. J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/head.12725","article-title":"Migraine triggers and oxidative stress: A narrative review and synthesis","volume":"56","author":"Borkum","year":"2016","journal-title":"Headache"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1021\/cn500083e","article-title":"Targeting TRP channels for novel migraine therapeutics","volume":"5","author":"Dussor","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1111\/bph.12512","article-title":"The TRPA1 channel in migraine mechanism and treatment","volume":"171","author":"Benemei","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e27426","DOI":"10.1016\/j.heliyon.2024.e27426","article-title":"Association between oxidative balance score and self-reported severe headache or migraine based on NHANES 1999 to 2004 data: A cross-sectional study","volume":"10","author":"Liu","year":"2024","journal-title":"Heliyon"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.neuroscience.2013.09.002","article-title":"Cortical spreading depression induces oxidative stress in the trigeminal nociceptive system","volume":"253","author":"Shatillo","year":"2013","journal-title":"Neuroscience"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s10194-019-0978-z","article-title":"ROS\/TRPA1\/CGRP signaling mediates cortical spreading depression","volume":"20","author":"Jiang","year":"2019","journal-title":"J. Headache Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/head.13214","article-title":"The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative Stress: Preliminary Evidence for a Theory","volume":"58","author":"Borkum","year":"2018","journal-title":"Headache"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4103\/1673-5374.230275","article-title":"Harnessing migraines for neural regeneration","volume":"13","author":"Borkum","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1007\/s11064-021-03335-9","article-title":"Brain Energy Deficit as a Source of Oxidative Stress in Migraine: A Molecular Basis for Migraine Susceptibility","volume":"46","author":"Borkum","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, Y., Yue, G., and Zhao, Y. (2023). Energy metabolism disturbance in migraine: From a mitochondrial point of view. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1133528"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Nikolova, S., and Schwedt, T.J. (2022). Magnetic resonance spectroscopy studies in migraine. Neurobiol. Pain, 12.","DOI":"10.1016\/j.ynpai.2022.100102"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Grech, O., Mollan, S.P., Wakerley, B.R., Fulton, D., Lavery, G.G., and Sinclair, A.J. (2021). The Role of Metabolism in Migraine Pathophysiology and Susceptibility. Life, 11.","DOI":"10.3390\/life11050415"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1177\/0333102410394675","article-title":"31P-MRS demonstrates a reduction in high-energy phosphates in the occipital lobe of migraine without aura patients","volume":"31","author":"Reyngoudt","year":"2011","journal-title":"Cephalalgia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/j.1468-2982.2005.01059.x","article-title":"Mitochondrial dysfunction and migraine: Evidence and hypotheses","volume":"26","author":"Sparaco","year":"2006","journal-title":"Cephalalgia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S0361-9230(01)00440-3","article-title":"Deficient energy metabolism is associated with low free magnesium in the brains of patients with migraine and cluster headache","volume":"54","author":"Lodi","year":"2001","journal-title":"Brain Res. Bull."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1177\/0333102412452048","article-title":"Magnetic resonance spectroscopy in migraine: What have we learned so far?","volume":"32","author":"Reyngoudt","year":"2012","journal-title":"Cephalalgia"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1080\/00207454.2017.1374959","article-title":"A study of oxidative stress in migraine with special reference to prophylactic therapy","volume":"128","author":"Tripathi","year":"2018","journal-title":"Int. J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1089\/gtmb.2014.0037","article-title":"DNA repair gene variants in migraine","volume":"18","author":"Cetinkaya","year":"2014","journal-title":"Genet. Test. Mol. Biomarkers"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1177\/10738584221090836","article-title":"DNA Damage and Repair in Migraine: Oxidative Stress and Beyond","volume":"29","author":"Fila","year":"2022","journal-title":"Neuroscientist"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"233","DOI":"10.4103\/aian.AIAN_229_19","article-title":"Vitamin D Deficiency and Its Correlates in Migraine Patients","volume":"23","author":"Seo","year":"2020","journal-title":"Ann. Indian Acad. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"366","DOI":"10.3988\/jcn.2018.14.3.366","article-title":"Effect of Vitamin D Deficiency on the Frequency of Headaches in Migraine","volume":"14","author":"Song","year":"2018","journal-title":"J. Clin. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.nutres.2023.11.008","article-title":"Vitamin B(6) and folate intake are associated with lower risk of severe headache or migraine in adults: An analysis based on NHANES 1999\u20132004","volume":"121","author":"Tian","year":"2024","journal-title":"Nutr. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7286737","DOI":"10.1155\/2019\/7286737","article-title":"Pro- and Antioxidant Effects of Vitamin C in Cancer in correspondence to Its Dietary and Pharmacological Concentrations","volume":"2019","author":"Pawlowska","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1080\/14737175.2021.1951236","article-title":"The role of a potential biomarker in patients with migraine: Review and new insights","volume":"21","author":"Ferreira","year":"2021","journal-title":"Expert Rev. Neurother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/112_2014_18","article-title":"The TRPA1 channel in inflammatory and neuropathic pain and migraine","volume":"167","author":"Nassini","year":"2014","journal-title":"Rev. Physiol. Biochem. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, S., Takahashi, N., Chen, C., Pauli, J., Kuroki, C., Kaminosono, J., Kashiwadani, H., Kanmura, Y., Mori, Y., and Ou, S. (2020). Article 576209 T (2020) Transient Receptor Potential Ankyrin 1 Mediates Hypoxic Responses in Mice. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.576209"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nature14367","article-title":"Structure of the TRPA1 ion channel suggests regulatory mechanisms","volume":"520","author":"Paulsen","year":"2015","journal-title":"Nature"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1039\/b801481g","article-title":"A primer on ankyrin repeat function in TRP channels and beyond","volume":"4","author":"Gaudet","year":"2008","journal-title":"Mol. Biosyst."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41421-023-00527-1","article-title":"Molecular architecture and gating mechanisms of the Drosophila TRPA1 channel","volume":"9","author":"Wang","year":"2023","journal-title":"Cell Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1002\/bies.201500085","article-title":"How the TRPA1 receptor transmits painful stimuli: Inner workings revealed by electron cryomicroscopy","volume":"37","author":"Brewster","year":"2015","journal-title":"BioEssays"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1152\/physrev.00005.2019","article-title":"Mammalian Transient Receptor Potential TRPA1 Channels: From Structure to Disease","volume":"100","author":"Talavera","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/978-981-10-7757-9_6","article-title":"Transient Receptor Potential (TRP) Channels","volume":"87","author":"Samanta","year":"2018","journal-title":"Sub-Cell. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00232-023-00277-x","article-title":"Research Progress on TRPA1 in Diseases","volume":"256","author":"Li","year":"2023","journal-title":"J. Membr. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"26331055231220340","DOI":"10.1177\/26331055231220340","article-title":"A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain","volume":"18","author":"Anand","year":"2023","journal-title":"Neurosci. Insights"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/bcpt.12138","article-title":"TRPA1: A transducer and amplifier of pain and inflammation","volume":"114","author":"Koivisto","year":"2014","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"700","DOI":"10.3390\/ijms24010700","article-title":"TRP Channels: Recent Development in Translational Research and Potential Therapeutic Targets in Migraine","volume":"24","author":"Spekker","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Yao, K., Dou, B., Zhang, Y., Chen, Z., Li, Y., Fan, Z., Ma, Y., Du, S., Wang, J., and Xu, Z. (2023). Inflammation-the role of TRPA1 channel. Front. Physiol., 14.","DOI":"10.3389\/fphys.2023.1093925"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1523\/JNEUROSCI.5369-07.2008","article-title":"Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress","volume":"28","author":"Andersson","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s10194-017-0804-4","article-title":"The role of the transient receptor potential ankyrin type-1 (TRPA1) channel in migraine pain: Evaluation in an animal model","volume":"18","author":"Demartini","year":"2017","journal-title":"J. Headache Pain"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"13525","DOI":"10.1073\/pnas.0705924104","article-title":"TRPA1 mediates formalin-induced pain","volume":"104","author":"McNamara","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1080\/14728222.2020.1815191","article-title":"TRPA1 as a therapeutic target for nociceptive pain","volume":"24","author":"Nassini","year":"2020","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Al-Karagholi, M.A., Kalatharan, V., Fagerberg, P.S., and Amin, F.M. (2023). The vascular role of CGRP: A systematic review of human studies. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1204734"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4796","DOI":"10.1093\/brain\/awad390","article-title":"CGRP signalling in migraine: Time to look downstream?","volume":"146","author":"Levy","year":"2023","journal-title":"Brain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/313054a0","article-title":"Calcitonin gene-related peptide is a potent vasodilator","volume":"313","author":"Brain","year":"1985","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1517\/13543784.10.4.673","article-title":"Substance P receptor antagonists in the therapy of migraine","volume":"10","author":"May","year":"2001","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1161\/CIRCRESAHA.108.189530","article-title":"Endothelium-dependent cerebral artery dilation mediated by TRPA1 and Ca2+-Activated K+ channels","volume":"104","author":"Earley","year":"2009","journal-title":"Circ. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"ra2","DOI":"10.1126\/scisignal.2005659","article-title":"Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation","volume":"8","author":"Sullivan","year":"2015","journal-title":"Sci. Signal."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.1038\/ncomms6732","article-title":"TRPA1 is essential for the vascular response to environmental cold exposure","volume":"5","author":"Aubdool","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Zhang, S., Azubuine, J., and Schmeer, C. (2023). A systematic literature review on the role of glial cells in the pathomechanisms of migraine. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1219574"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"5424","DOI":"10.1172\/JCI128022","article-title":"Schwann cells expressing nociceptive channel TRPA1 orchestrate ethanol-evoked neuropathic pain in mice","volume":"129","author":"Landini","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1089\/ars.2013.5616","article-title":"Redox regulation of transient receptor potential channels","volume":"21","author":"Kozai","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.freeradbiomed.2019.10.415","article-title":"Transient receptor potential (TRP) channels: Biosensors for redox environmental stimuli and cellular status","volume":"146","author":"Sakaguchi","year":"2020","journal-title":"Free Radical Biol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Moccia, F., and Montagna, D. (2023). Transient Receptor Potential Ankyrin 1 (TRPA1) Channel as a Sensor of Oxidative Stress in Cancer Cells. Cells, 12.","DOI":"10.3390\/cells12091261"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ccell.2020.06.001","article-title":"Oxidative Stress in Cancer","volume":"38","author":"Hayes","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.ccell.2018.05.001","article-title":"Cancer Cells Co-opt the Neuronal Redox-Sensing Channel TRPA1 to Promote Oxidative-Stress Tolerance","volume":"33","author":"Takahashi","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41420-023-01530-x","article-title":"Transient receptor potential ankyrin 1 (TRPA1) mediates reactive oxygen species-induced Ca(2+) entry, mitochondrial dysfunction, and caspase-3\/7 activation in primary cultures of metastatic colorectal carcinoma cells","volume":"9","author":"Faris","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.3892\/etm.2021.10897","article-title":"Transient receptor potential ankyrin 1 and calcium: Interactions and association with disease (Review)","volume":"22","author":"Hu","year":"2021","journal-title":"Exp. Ther. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"32691","DOI":"10.1074\/jbc.M803568200","article-title":"The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions","volume":"283","author":"Wang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1177\/0960327119877460","article-title":"TRPA1 and issues relating to animal model selection for extrapolating toxicity data to humans","volume":"39","author":"Lindsay","year":"2019","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.neuron.2019.11.023","article-title":"Structural Insights into Electrophile Irritant Sensing by the Human TRPA1 Channel","volume":"105","author":"Suo","year":"2020","journal-title":"Neuron"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.cub.2005.04.018","article-title":"The pungency of garlic: Activation of TRPA1 and TRPV1 in response to allicin","volume":"15","author":"Macpherson","year":"2005","journal-title":"Curr. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"19564","DOI":"10.1073\/pnas.0609598103","article-title":"TRP channel activation by reversible covalent modification","volume":"103","author":"Hinman","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nchembio.640","article-title":"TRPA1 underlies a sensing mechanism for O2","volume":"7","author":"Takahashi","year":"2011","journal-title":"Nat. Chem. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1124\/mol.112.084194","article-title":"Benzoquinone reveals a cysteine-dependent desensitization mechanism of TRPA1","volume":"83","author":"Ibarra","year":"2013","journal-title":"Mol. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"6169","DOI":"10.1074\/jbc.M111.329748","article-title":"Identification of in vivo disulfide conformation of TRPA1 ion channel","volume":"287","author":"Wang","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1085\/jgp.201711876","article-title":"Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition","volume":"150","author":"Samanta","year":"2018","journal-title":"J. Gen. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s12272-013-0098-2","article-title":"Emerging roles of TRPA1 in sensation of oxidative stress and its implications in defense and danger","volume":"36","author":"Kim","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"31962","DOI":"10.1074\/jbc.M112.361139","article-title":"Hypoxia-inducible factor-1\u03b1 (HIF1\u03b1) switches on transient receptor potential ankyrin repeat 1 (TRPA1) gene expression via a hypoxia response element-like motif to modulate cytokine release","volume":"287","author":"Hatano","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_87","first-page":"e60629","article-title":"Evaluation of Oxidative Stress and Antioxidant Biomarkers in Chronic Cigarette Smokers: A Pilot Study","volume":"16","author":"Pandi","year":"2024","journal-title":"Cureus"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s11916-023-01103-8","article-title":"The Relationship of Tobacco Use and Migraine: A Narrative Review","volume":"27","author":"Weinberger","year":"2023","journal-title":"Curr. Pain Headache Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"b3914","DOI":"10.1136\/bmj.b3914","article-title":"Migraine and cardiovascular disease: Systematic review and meta-analysis","volume":"339","author":"Rist","year":"2009","journal-title":"BMJ"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Pizzimenti, S., Ciamporcero, E., Daga, M., Pettazzoni, P., Arcaro, A., Cetrangolo, G., Minelli, R., Dianzani, C., Lepore, A., and Gentile, F. (2013). Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Front. Physiol., 4.","DOI":"10.3389\/fphys.2013.00242"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.taap.2016.08.028","article-title":"Role of TRPA1 in acute cardiopulmonary toxicity of inhaled acrolein","volume":"324","author":"Conklin","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.taap.2016.10.008","article-title":"TRPA1 mediates changes in heart rate variability and cardiac mechanical function in mice exposed to acrolein","volume":"324","author":"Kurhanewicz","year":"2017","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/j.cell.2006.02.023","article-title":"TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents","volume":"124","author":"Bautista","year":"2006","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"L812","DOI":"10.1152\/ajplung.00164.2015","article-title":"Cigarette smoke has sensory effects through nicotinic and TRPA1 but not TRPV1 receptors on the isolated mouse trachea and larynx","volume":"309","author":"Kichko","year":"2015","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.pain.2010.08.021","article-title":"TRPA1 receptors mediate environmental irritant-induced meningeal vasodilatation","volume":"152","author":"Kunkler","year":"2011","journal-title":"Pain"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1177\/096032719601500601","article-title":"Acute effects of the potent lacrimator o-chlorobenzylidene malononitrile (CS) tear gas","volume":"15","author":"Anderson","year":"1996","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.redox.2016.12.035","article-title":"Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress","volume":"11","author":"Sies","year":"2017","journal-title":"Redox Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1093\/brain\/awy177","article-title":"TRPA1\/NOX in the soma of trigeminal ganglion neurons mediates migraine-related pain of glyceryl trinitrate in mice","volume":"141","author":"Marone","year":"2018","journal-title":"Brain"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1097\/00019052-200106000-00009","article-title":"Nitric oxide in primary headaches","volume":"14","author":"Thomsen","year":"2001","journal-title":"Curr. Opin. Neurol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.pharmthera.2008.08.003","article-title":"The role of nitric oxide (NO) in migraine, tension-type headache and cluster headache","volume":"120","author":"Olesen","year":"2008","journal-title":"Pharmacol. Ther."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/sj.bjp.0704842","article-title":"Nitric oxide synthase inhibitors can antagonize neurogenic and calcitonin gene-related peptide induced dilation of dural meningeal vessels","volume":"137","author":"Akerman","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1111\/j.1460-9568.2006.04742.x","article-title":"Nitric oxide regulation of calcitonin gene-related peptide gene expression in rat trigeminal ganglia neurons","volume":"23","author":"Bellamy","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1038\/ncomms5381","article-title":"H2S and NO cooperatively regulate vascular tone by activating a neuroendocrine HNO-TRPA1-CGRP signalling pathway","volume":"5","author":"Eberhardt","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1159\/000121407","article-title":"Selective Arterial Dilatation by Glyceryl Trinitrate Is Not Associated with Nitric Oxide Formation in vitro","volume":"45","author":"Miller","year":"2008","journal-title":"J. Vasc. Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1038\/nn1902","article-title":"Cortical spreading depression causes and coincides with tissue hypoxia","volume":"10","author":"Takano","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1111\/bph.13917","article-title":"The anti-migraine component of butterbur extracts, isopetasin, desensitizes peptidergic nociceptors by acting on TRPA1 cation channel","volume":"174","author":"Benemei","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1212\/WNL.0000000000004391","article-title":"Erenumab (AMG 334) in episodic migraine: Interim analysis of an ongoing open-label study","volume":"89","author":"Ashina","year":"2017","journal-title":"Neurology"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Benemei, S., and Dussor, G. (2019). TRP Channels and Migraine: Recent Developments and New Therapeutic Opportunities. Pharmaceuticals, 12.","DOI":"10.3390\/ph12020054"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1111\/head.13417","article-title":"Anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: Update on a Previous Review After the American Headache Society 60th Scientific Meeting, San Francisco, June 2018","volume":"58","author":"Tepper","year":"2018","journal-title":"Headache"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.neuron.2015.11.001","article-title":"G Protein-Coupled Receptors: Dynamic Machines for Signaling Pain and Itch","volume":"88","author":"Geppetti","year":"2015","journal-title":"Neuron"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev-physiol-030212-183811","article-title":"TRPA1: A gatekeeper for inflammation","volume":"75","author":"Bautista","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.csbj.2019.08.005","article-title":"G Protein-Coupled Receptor Systems and Their Role in Cellular Senescence","volume":"17","author":"Leysen","year":"2019","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s40122-021-00240-5","article-title":"Structural and Functional Brain Changes in Migraine","volume":"10","author":"Ashina","year":"2021","journal-title":"Pain Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1161\/01.STR.0000206446.26702.e9","article-title":"Brain stem and cerebellar hyperintense lesions in migraine","volume":"37","author":"Kruit","year":"2006","journal-title":"Stroke"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1111\/j.1468-2982.2009.01904.x","article-title":"Migraine is associated with an increased risk of deep white matter lesions, subclinical posterior circulation infarcts and brain iron accumulation: The population-based MRI CAMERA study","volume":"30","author":"Kruit","year":"2010","journal-title":"Cephalalgia"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s10194-023-01648-4","article-title":"Headache disorders and relevant sex and socioeconomic patterns in adolescents and young adults across 204 countries and territories: An updated global analysis","volume":"24","author":"Ge","year":"2023","journal-title":"J. Headache Pain"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Persoons, E., Kerselaers, S., Voets, T., Vriens, J., and Held, K. (2021). Partial Agonistic Actions of Sex Hormone Steroids on TRPM3 Function. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413652"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Artero-Morales, M., Gonz\u00e1lez-Rodr\u00edguez, S., and Ferrer-Montiel, A. (2018). TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain. Front. Mol. Biosci., 5.","DOI":"10.3389\/fmolb.2018.00073"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"108297","DOI":"10.1016\/j.pharmthera.2022.108297","article-title":"ThermoTRP channels in pain sexual dimorphism: New insights for drug intervention","volume":"240","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Lemos, C., Alonso, I., Barros, J., Sequeiros, J., Pereira-Monteiro, J., Mendon\u00e7a, D., and Sousa, A. (2012). Assessing risk factors for migraine: Differences in gender transmission. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050626"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Guo, X., Wang, D., Ying, C., and Hong, Y. (2023). Association between brain structures and migraine: A bidirectional Mendelian randomization study. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1148458"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/14\/3385\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:19:18Z","timestamp":1760109558000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/14\/3385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,18]]},"references-count":121,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["molecules29143385"],"URL":"https:\/\/doi.org\/10.3390\/molecules29143385","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,18]]}}}