Elucidating Novel Therapeutic Targets for Oropharyngeal Dysphagia: Focusing on TRPA1 and TRPV4 Channels

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In this project we investigate the involvement of TRPA1 and TRPV4 in swallowing reflex. We observed TRPA1 and TRPV4 expression on afferent neurons of the swallowing-related regions. TRPA1 localized majorly on small to medium diameter neurons and TRPV4 majorly localized on large to medium diameter neurons. We also observed that topical application of a chemical agonist for TRPA1, allyl isothiocyanate (AITC) or agonist for TRPV4, GSK1016790A, in the swallowing-related regions dose-dependently facilitated the triggering of swallowing reflex. Prior topical application of antagonists for TRPA1 or TRPV4 significantly reduced the AITC or GSK1016790A-induced swallowing reflex, respectively. Application of cold AITC (4 °C) very briefly reduced the on-site temperature to <17 °C (temperature at which TRPA1s can be activated), but had no effect on triggering of the reflex. By contrast, reducing the on-site temperature to <17 °C for a longer time by continuous flow of cold AITC or by application of iced AITC paradoxically delayed/prevented the triggering of AITC-induced reflexes. Prior application of the TRPA1 antagonist had no effect on the threshold for the punctate mechanical stimuli-induced reflex or the number of low-force or high-force continuous mechanical pressure stimuli-induced reflexes. We have published these data in "Scientific Reports" and "Front. Cell. Neurosci." journals. Now we are conducting research on the involvement of TRPV4 in water-induced swallowing reflex.