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The aim of this study was to assess the acute therapeutic effect of TRPA1\/M8 agonists in improving swallowing function in OD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty\u2010eight patients with OD caused by aging, stroke, or neurodegenerative disease were included in a three\u2010arm, quadruple\u2010blind, randomized clinical trial (NCT02193438). Swallowing safety and efficacy and the kinematics of the swallow response were assessed by videofluoroscopy (VFS) during the swallow of 182\u00a0\u00b1\u00a02\u00a0mPa\u00b7s viscosity (nectar) boluses of a xanthan gum thickener supplemented with (a) 756.6\u00a0\u03bcmol\/L cinnamaldehyde and 70\u00a0\u03bcmol\/L zinc (CIN\u2010Zn) (TRPA1 agonists), (b) 1.6\u00a0mmol\/L citral (CIT) (TRPA1 agonist), or (c) 1.6\u00a0mmol\/L citral and 1.3\u00a0mmol\/L isopulegol (CIT\u2010ISO) (TRPA1 and TRPM8 agonists). The effects on pharyngeal event\u2010related potentials (ERP) were assessed by electroencephalography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>TRPA1 stimulation with either CIN\u2010Zn or CIT reduced time to laryngeal vestibule closure (CIN\u2010Zn <jats:italic>P<\/jats:italic>\u00a0=\u00a0.002, CIT <jats:italic>P<\/jats:italic>\u00a0=\u00a0.023) and upper esophageal sphincter opening (CIN\u2010Zn <jats:italic>P<\/jats:italic>\u00a0=\u00a0.007, CIT <jats:italic>P<\/jats:italic>\u00a0=\u00a0.035). In addition, CIN\u2010Zn reduced the penetration\u2010aspiration scale score (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.009), increased the prevalence of safe swallows (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.041), and reduced the latency of the P2 peak of the ERP. CIT\u2010ISO had no positive effect on biomechanics or neurophysiology. No significant adverse events were observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Inferences<\/jats:title><jats:p>TRPA1 stimulation with CIN\u2010Zn or CIT improves the swallow response which, in the case of CIN\u2010Zn, is associated with a significant improvement in cortical activation and safety of swallow. These results provide the basis for the development of new active treatments for OD using TRPA1 agonists.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.13821","type":"journal-article","created":{"date-parts":[[2020,2,17]],"date-time":"2020-02-17T06:00:15Z","timestamp":1581919215000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["A randomized clinical trial on the acute therapeutic effect of TRPA1 and TRPM8 agonists in patients with oropharyngeal dysphagia"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7149-7948","authenticated-orcid":false,"given":"Noem\u00ed","family":"Tomsen","sequence":"first","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas Instituto de Salud Carlos III Barcelona Spain"},{"name":"Gastrointestinal Motility Laboratory Hospital de Matar\u00f3 Consorci Sanitari del Maresme Matar\u00f3 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