Abstract
We examined the role of TRPA1s in triggering the swallowing reflex. TRPA1s predominantly localized on thin nerve fibers and fibroblast-like cells in swallowing-related regions and on small to medium-sized superior laryngeal nerve-afferents in the nodose–petrosal–jugular ganglionic complex. Topical application of a TRPA1 agonist, allyl isothiocyanate (AITC), dose-dependently triggered swallowing reflexes. Prior topical application of a TRPA1 antagonist significantly attenuated the AITC-induced reflexes. 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. TRPA1s are functional and act as chemosensors, but not as cold sensors or mechanosensors, for triggering of the swallowing reflex. A brief cold stimulus has no effect on triggering of the reflex. However, a longer cold stimulus delays/prevents triggering of the reflex because of cold anesthesia.
Highlights
We examined the role of TRPA1s in triggering the swallowing reflex
TRPA1s are predominantly localized on thin nerve fibers and fibroblast‐like cells in the superior laryngeal nerve (SLN)‐innervated swallowing‐related regions
We examined the effect of the TRPA1 antagonist on the number and interval of the swallowing reflexes induced by delivery of saline (250 μL at room temperature) continuously for 4 s to assess the contribution of TRPA1s in saline-induced swallowing reflexes
Summary
We examined the role of TRPA1s in triggering the swallowing reflex. TRPA1s predominantly localized on thin nerve fibers and fibroblast-like cells in swallowing-related regions and on small to mediumsized superior laryngeal nerve-afferents in the nodose–petrosal–jugular ganglionic complex. 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. TRPA1s are functional and act as chemosensors, but not as cold sensors or mechanosensors, for triggering of the swallowing reflex. The sensory inputs from the pharyngeal and laryngeal regions play an important role to activate the swallowing central pattern generator (sCPG) located in the brainstem in triggering the swallowing r eflex[1–4]. Understanding the role of TRPA1s in triggering of the swallowing reflex is important for developing therapeutics to manage dysphagia In this context, a recent clinical study reported that TRPA1 agonists improved the swallowing response in patients with oropharyngeal dysphagia associated with aging, stroke, and neurodegenerative diseases[24]
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