{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T21:27:23Z","timestamp":1781558843376,"version":"3.54.5"},"reference-count":95,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T00:00:00Z","timestamp":1678492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, the transient receptor potential ankyrin 1 (TRPA1) has gained more attention in migraine-related research. The involvement of the TRPA1 receptor in migraine headaches is proposed by the fact that TRPA1 may be a target of some migraine-triggering factors. Although it is doubtful that activation of TRPA1 alone is sufficient to induce pain, behavioral studies have demonstrated that TRPA1 is involved in injury- and inflammation-induced hypersensitivity. Here, we review the functional relevance of TRPA1 in headaches and its therapeutic potential, mainly focusing on its role in the development of hypersensitivity, referring to its altered expression in pathological conditions, and its functional interaction with other TRP channels.<\/jats:p>","DOI":"10.3390\/ijms24065375","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T05:36:21Z","timestamp":1678685781000},"page":"5375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Modification of the TRP Channel TRPA1 as a Relevant Factor in Migraine-Related Intracranial Hypersensitivity"],"prefix":"10.3390","volume":"24","author":[{"given":"Thannoon","family":"Masood","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szandra","family":"Lakatos","sequence":"additional","affiliation":[{"name":"Department of Physiology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Rosta","sequence":"additional","affiliation":[{"name":"Department of Physiology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.ncl.2019.06.001","article-title":"Migraine: Epidemiology, Burden, and Comorbidity","volume":"37","author":"Burch","year":"2019","journal-title":"Neurol. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/j.1526-4610.1988.hed2802124.x","article-title":"Common migraine: Criteria for diagnosis","volume":"28","author":"Solomon","year":"1988","journal-title":"Headache"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1038\/s41598-021-82080-z","article-title":"Prevalence and characteristics of cutaneous allodynia in probable migraine","volume":"11","author":"Han","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1036798","DOI":"10.3389\/fneur.2022.1036798","article-title":"Autonomic symptoms in migraine: Results of a prospective longitudinal study","volume":"13","author":"Ray","year":"2022","journal-title":"Front. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/j.1526-4610.1991.hed3109582.x","article-title":"Sustained visual aura: A totally new variation of migraine","volume":"31","author":"Luda","year":"1991","journal-title":"Headache"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1136\/jnnp.44.9.846","article-title":"Asymmetry of the aura and pain in migraine","volume":"44","author":"Peatfield","year":"1981","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1093\/ije\/24.3.612","article-title":"Prevalence and sex-ratio of the subtypes of migraine","volume":"24","author":"Russell","year":"1995","journal-title":"Int. J. Epidemiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1046\/j.1468-2982.1992.1204221.x","article-title":"Migraine with aura and migraine without aura: An epidemiological study","volume":"12","author":"Rasmussen","year":"1992","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_9","first-page":"65","article-title":"Classification and diagnostic criteria for primary headache disorders (Ad Hoc Committee IHS, 1988)","volume":"4","author":"Nappi","year":"1989","journal-title":"Funct. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1098-3597(99)90035-2","article-title":"Classification and epidemiology of headache","volume":"1","author":"Lipton","year":"1999","journal-title":"Clin. Cornerstone"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1212\/WNL.10.6.555","article-title":"The tentorial nerves and Iocalization of intracranial pain in man","volume":"10","author":"Feindel","year":"1960","journal-title":"Neurology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/ana.410160202","article-title":"The neurobiology of vascular head pain","volume":"16","author":"Moskowitz","year":"1984","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1007\/BF01642901","article-title":"Neuroeffector functions of sensory fibres: Implications for headache mechanisms and drug actions","volume":"238","author":"Moskowitz","year":"1991","journal-title":"J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1111\/j.1468-2982.2005.01025.x","article-title":"Implication of augmented vasogenic leakage in the mechanism of persistent aura in sporadic hemiplegic migraine","volume":"26","author":"Iizuka","year":"2006","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2038","DOI":"10.1212\/WNL.0000000000007371","article-title":"Imaging of neuroinflammation in migraine with aura: A [11C]PBR28 PET\/MRI study","volume":"92","author":"Albrecht","year":"2019","journal-title":"Neurology"},{"key":"ref_16","first-page":"142","article-title":"What is a nociceptor?","volume":"46","author":"Messlinger","year":"1997","journal-title":"Anaesthesist"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/384560a0","article-title":"Sensitization of meningeal sensory neurons and the origin of headaches","volume":"384","author":"Strassman","year":"1996","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1177\/0333102415574845","article-title":"Sensitization of the Trigeminovascular System following Environmental Irritant Exposure","volume":"35","author":"Kunkler","year":"2015","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/18906","article-title":"A capsaicin-receptor homologue with a high threshold for noxious heat","volume":"398","author":"Caterina","year":"1999","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1523\/JNEUROSCI.4745.04.2005","article-title":"Altered thermal selection behavior in mice lacking transient receptor potential vanilloid 4","volume":"25","author":"Lee","year":"2005","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nature05910","article-title":"The menthol receptor TRPM8 is the principal detector of environmental cold","volume":"448","author":"Bautista","year":"2007","journal-title":"Nature"},{"key":"ref_22","first-page":"re3","article-title":"The TRP superfamily of cation channels","volume":"2005","author":"Montell","year":"2005","journal-title":"Sci. STKE Signal Transduct. Knowl. Environ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/S0092-8674(03)00158-2","article-title":"ANKTM1, a TRP-like Channel Expressed in Nociceptive Neurons, Is Activated by Cold Temperatures","volume":"112","author":"Story","year":"2003","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1073\/pnas.0808487106","article-title":"TRPA1 acts as a cold sensor in vitro and in vivo","volume":"106","author":"Karashima","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1002\/cne.20794","article-title":"Distinct expression of TRPM8, TRPA1, and TRPV1 mRNAs in rat primary afferent neurons with adelta\/c-fibers and colocalization with trk receptors","volume":"493","author":"Kobayashi","year":"2005","journal-title":"J. Comp. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nature02282","article-title":"Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1","volume":"427","author":"Jordt","year":"2004","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/S0896-6273(04)00150-3","article-title":"Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin","volume":"41","author":"Bandell","year":"2004","journal-title":"Neuron"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1111\/j.1460-9568.2004.03695.x","article-title":"Two populations of cold-sensitive neurons in rat dorsal root ganglia and their modulation by nerve growth factor","volume":"20","author":"Babes","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1097\/j.pain.0000000000000979","article-title":"Dose-response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation","volume":"158","author":"Andersen","year":"2017","journal-title":"Pain"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.neuron.2010.04.030","article-title":"A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome","volume":"66","author":"Kremeyer","year":"2010","journal-title":"Neuron"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1097\/j.pain.0000000000001660","article-title":"Epidermal expression of human TRPM8, but not of TRPA1 ion channels, is associated with sensory responses to local skin cooling","volume":"160","author":"Pinter","year":"2019","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1172\/JCI25437","article-title":"TRPA1 induced in sensory neurons contributes to cold hyperalgesia after inflammation and nerve injury","volume":"115","author":"Obata","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"249","DOI":"10.3389\/fphys.2015.00249","article-title":"TRPA1 mediates amplified sympathetic responsiveness to activation of metabolically sensitive muscle afferents in rats with femoral artery occlusion","volume":"6","author":"Xing","year":"2015","journal-title":"Front. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1111\/j.1365-2982.2007.00939.x","article-title":"Stimulation of neuronal receptors, neuropeptides and cytokines during experimental oil of mustard colitis","volume":"19","author":"Kimball","year":"2007","journal-title":"Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1136\/thoraxjnl-2011-201443","article-title":"Transient receptor potential channels mediate the tussive response to prostaglandin E2 and bradykinin","volume":"67","author":"Grace","year":"2012","journal-title":"Thorax"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1111\/j.1460-9568.2007.05882.x","article-title":"Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation","volume":"26","author":"Bang","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"ref_37","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_38","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12931-019-1060-8","article-title":"Bradykinin sensitizes the cough reflex via a B2 receptor dependent activation of TRPV1 and TRPA1 channels through metabolites of cyclooxygenase and 12-lipoxygenase","volume":"20","year":"2019","journal-title":"Respir. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.expneurol.2006.01.031","article-title":"Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats","volume":"200","author":"Katsura","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuroscience.2020.09.048","article-title":"Thermal Hyperalgesia and Mechanical Allodynia Elicited by Histamine and Non-histaminergic Itch Mediators: Respective Involvement of TRPV1 and TRPA1","volume":"449","author":"Tsagareli","year":"2020","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Miyano, K., Shiraishi, S., Minami, K., Sudo, Y., Suzuki, M., Yokoyama, T., Terawaki, K., Nonaka, M., Murata, H., and Higami, Y. (2019). Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways. Int. J. Mol. Sci., 20.","DOI":"10.20944\/preprints201906.0155.v1"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/brain\/awac273","article-title":"TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy","volume":"146","author":"Marcotti","year":"2023","journal-title":"Brain J. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1111\/ejn.15062","article-title":"The ubiquitin E3 ligase Nedd4-2 relieves mechanical allodynia through the ubiquitination of TRPA1 channel in db\/db mice","volume":"53","author":"Wang","year":"2021","journal-title":"Eur. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1744806920925425","DOI":"10.1177\/1744806920925425","article-title":"Satellite glial cells in sensory ganglia express functional transient receptor potential ankyrin 1 that is sensitized in neuropathic and inflammatory pain","volume":"16","author":"Shin","year":"2020","journal-title":"Mol. Pain"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/WNR.0000000000001862","article-title":"Knockout of transient receptor potential ankyrin 1 (TRPA1) modulates the glial phenotype and alleviates perihematomal neuroinflammation after intracerebral hemorrhage in mice via MAPK\/NF-\u03baB signaling","volume":"34","author":"Xia","year":"2023","journal-title":"Neuroreport"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Demartini, C., Greco, R., Magni, G., Zanaboni, A.M., Riboldi, B., Francavilla, M., Nativi, C., Ceruti, S., and Tassorelli, C. (2022). Modulation of Glia Activation by TRPA1 Antagonism in Preclinical Models of Migraine. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214085"},{"key":"ref_47","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_48","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1523\/JNEUROSCI.0013-05.2005","article-title":"Nociceptor and Hair Cell Transducer Properties of TRPA1, a Channel for Pain and Hearing","volume":"25","author":"Nagata","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/j.pain.2012.06.012","article-title":"Activation of TRPA1 on dural afferents: A potential mechanism of headache pain","volume":"153","author":"Edelmayer","year":"2012","journal-title":"Pain"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/1744-8069-8-66","article-title":"Expression of the transient receptor potential channels TRPV1, TRPA1 and TRPM8 in mouse trigeminal primary afferent neurons innervating the dura","volume":"8","author":"Huang","year":"2012","journal-title":"Mol. Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/j.1365-2125.1989.tb05424.x","article-title":"A comparison of the effects of human alpha calcitonin gene-related peptide and glyceryl trinitrate on regional blood velocity in man","volume":"28","author":"MacDonald","year":"1989","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/ana.410330109","article-title":"The trigeminovascular system and migraine: Studies characterizing cerebrovascular and neuropeptide changes seen in humans and cats","volume":"33","author":"Goadsby","year":"1993","journal-title":"Ann. Neurol."},{"key":"ref_53","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 Int. J. Headache"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"34781","DOI":"10.1074\/jbc.M110.143958","article-title":"The General Anesthetic Propofol Excites Nociceptors by Activating TRPV1 and TRPA1 Rather than GABAA Receptors","volume":"285","author":"Fischer","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ejphar.2012.05.053","article-title":"The role of transient receptor potential ankyrin 1 (TRPA1) receptor activation in hydrogen-sulphide-induced CGRP-release and vasodilation","volume":"689","author":"Pozsgai","year":"2012","journal-title":"Eur. J. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.pharep.2019.02.015","article-title":"Effect of TRPA1 activator allyl isothiocyanate (AITC) on rat dural and pial arteries","volume":"71","author":"Hansted","year":"2019","journal-title":"Pharmacol. Rep. PR"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"140","DOI":"10.4103\/1673-5374.243719","article-title":"Effects of TRPA1 activation and inhibition on TRPA1 and CGRP expression in dorsal root ganglion neurons","volume":"14","author":"Wang","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1046\/j.1468-2982.1995.1504281.x","article-title":"Experimental headache in humans","volume":"15","author":"Iversen","year":"1995","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_59","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_60","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/j.1468-2982.2007.01303.x","article-title":"The triggers or precipitants of the acute migraine attack","volume":"27","author":"Kelman","year":"2007","journal-title":"Cephalalgia Int. J. Headache"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1111\/j.1526-4610.2009.01542.x","article-title":"Cluster headache as the result of secondhand cigarette smoke exposure during childhood","volume":"50","author":"Rozen","year":"2010","journal-title":"Headache"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.taap.2008.04.005","article-title":"Tear gasses CN, CR, and CS are potent activators of the human TRPA1 receptor","volume":"231","author":"Peeters","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_63","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_64","doi-asserted-by":"crossref","unstructured":"Miyamoto, T., Dubin, A.E., Petrus, M.J., and Patapoutian, A. (2009). TRPV1 and TRPA1 mediate peripheral nitric oxide-induced nociception in mice. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007596"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"13519","DOI":"10.1073\/pnas.0705923104","article-title":"4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1","volume":"104","author":"Trevisani","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","first-page":"22","article-title":"The hemodynamic analysis of cranial artery pulse wave contours in vascular headache of the migraine type","volume":"56","author":"Tunis","year":"1952","journal-title":"Trans. Am. Neurol. Assoc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/j.1526-4610.1989.hed2905282.x","article-title":"Hyperperfusion of cerebral cortex, thalamus and basal ganglia during spontaneously occurring migraine headaches","volume":"29","author":"Kobari","year":"1989","journal-title":"Headache"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1097\/00004647-200110000-00005","article-title":"Magnetic resonance angiography in facial and other pain: Neurovascular mechanisms of trigeminal sensation","volume":"21","author":"May","year":"2001","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/brain\/awr272","article-title":"The \u201cheadache tree\u201d via umbellulone and TRPA1 activates the trigeminovascular system","volume":"135","author":"Nassini","year":"2012","journal-title":"Brain J. Neurol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neuroscience.2018.04.025","article-title":"The Transient Receptor Potential Ankyrin Type 1 Plays a Critical Role in Cortical Spreading Depression","volume":"382","author":"Jiang","year":"2018","journal-title":"Neuroscience"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1744806919836570","DOI":"10.1177\/1744806919836570","article-title":"Role of intraganglionic transmission in the trigeminovascular pathway","volume":"15","author":"Zhang","year":"2019","journal-title":"Mol. Pain"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1126\/science.288.5464.306","article-title":"Impaired nociception and pain sensation in mice lacking the capsaicin receptor","volume":"288","author":"Caterina","year":"2000","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/35012076","article-title":"Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia","volume":"405","author":"Davis","year":"2000","journal-title":"Nature"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S0140-6736(03)12392-6","article-title":"Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency","volume":"361","author":"Chan","year":"2003","journal-title":"Lancet Lond. Engl."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1074\/jbc.M115.700278","article-title":"Functional and Structural Divergence in Human TRPV1 Channel Subunits by Oxidative Cysteine Modification","volume":"291","author":"Ogawa","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_76","first-page":"1238","article-title":"Activation of transient receptor potential vanilloid 1 by lipoxygenase metabolites depends on PKC phosphorylation","volume":"31","author":"Kumar","year":"2017","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1002\/ejp.2017","article-title":"Role of Src kinase in regulating protein kinase C mediated phosphorylation of TRPV1","volume":"26","author":"Robilotto","year":"2022","journal-title":"Eur. J. Pain Lond. Engl."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1152\/physrev.00001.2002","article-title":"TRP Channel Proteins and Signal Transduction","volume":"82","author":"Minke","year":"2002","journal-title":"Physiol. Rev."},{"key":"ref_79","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_80","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1007\/s00424-014-1497-z","article-title":"Direct evidence for functional TRPV1\/TRPA1 heteromers","volume":"466","author":"Fischer","year":"2014","journal-title":"Pfl\u00fcg. Arch.-Eur. J. Physiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature02196","article-title":"TRP channels as cellular sensors","volume":"426","author":"Clapham","year":"2003","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.neuron.2014.12.065","article-title":"Tmem100 Is a Regulator of TRPA1-TRPV1 Complex and Contributes to Persistent Pain","volume":"85","author":"Weng","year":"2015","journal-title":"Neuron"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Cort\u00e9s-Montero, E., Rodr\u00edguez-Mu\u00f1oz, M., Ruiz-Cantero, M.D.C., Cobos, E.J., S\u00e1nchez-Bl\u00e1zquez, P., and Garz\u00f3n-Ni\u00f1o, J. (2020). Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010229"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/1744-8069-4-48","article-title":"HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity","volume":"4","author":"Eid","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00424-009-0749-9","article-title":"Activation of TRPA1 channels by fenamate nonsteroidal anti-inflammatory drugs","volume":"459","author":"Hu","year":"2010","journal-title":"Pflug. Arch."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.pain.2011.01.049","article-title":"Selective blockade of TRPA1 channel attenuates pathological pain without altering noxious cold sensation or body temperature regulation","volume":"152","author":"Chen","year":"2011","journal-title":"Pain"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1021\/acs.jmedchem.2c01830","article-title":"Discovery of BAY-390, a Selective CNS Penetrant Chemical Probe as Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonist","volume":"66","author":"Mesch","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1111\/jcmm.14099","article-title":"TRPA1 mediates the antinociceptive properties of the constituent of Crocus sativus L., safranal","volume":"23","author":"Landini","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1097\/j.pain.0000000000000669","article-title":"Crotalphine desensitizes TRPA1 ion channels to alleviate inflammatory hyperalgesia","volume":"157","author":"Bressan","year":"2016","journal-title":"Pain"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1523\/JNEUROSCI.3048-18.2019","article-title":"A Human TRPA1-Specific Pain Model","volume":"39","author":"Heber","year":"2019","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1016\/j.pain.2013.08.002","article-title":"Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel","volume":"154","author":"Materazzi","year":"2013","journal-title":"Pain"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s00424-011-1021-7","article-title":"Ligustilide: A novel TRPA1 modulator","volume":"462","author":"Zhong","year":"2011","journal-title":"Pflug. Arch."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1212\/01.WNL.0000147290.68260.11","article-title":"Petasites hybridus root (butterbur) is an effective preventive treatment for migraine","volume":"63","author":"Lipton","year":"2004","journal-title":"Neurology"},{"key":"ref_94","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_95","doi-asserted-by":"crossref","unstructured":"Koivisto, A., Jalava, N., Bratty, R., and Pertovaara, A. (2018). TRPA1 Antagonists for Pain Relief. 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