TRPA1s act as chemosensors but not as cold sensors or mechanosensors to trigger the swallowing reflex in rats

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.

MrgprA3-expressing pruriceptors drive pruritogen-induced alloknesis through mechanosensitive Piezo2 channel

“…Although it is commonly accepted that TRPA1 is expressed by a subset of TRPV1 + nociceptors and acts as a chemosensor mediating both inflammatory and neuropathic pain as well as pruritogen-induced non-evoked spontaneous scratching, the role of TRPA1 in mechanosensation has been controversial (21)(22)(23)(24). We therefore investigated whether TRPA1 is also involved in pruritogen-induced mechanical itch.…”

Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats

“…Electromyogram (EMG) activity of the mylohyoid muscle was recorded to identify the swallowing reflex (Hossain et al, 2018(Hossain et al, , 2020b(Hossain et al, , 2022. The mylohyoid muscle and other infraand supra-hyoid muscles are activated during the triggering of the swallowing reflex (Jean, 2001;Yamamura et al, 2010).…”

“…A high amplitude activity event in the EMG signal corresponded to one swallowing reflex. Therefore, triggered swallowing reflexes were identified and counted using high-amplitude EMG of the mylohyoid muscle and by visual checking of laryngeal movements associated with reflex triggering (Hossain et al, 2018(Hossain et al, , 2020b(Hossain et al, , 2022. The examiners used a loudspeaker connected to the EMG signal to facilitate observation of mylohyoid muscle firing.…”

“…For calculating the swallowing interval, the initial 10 s was chosen because GSK1016790A-induced shortening of the interval was most prominent within this time. The interval between the start of high-amplitude EMG firing for one swallowing reflex and the beginning of high-amplitude EMG firing for the subsequent reflex was used as the interval between the reflexes (Hossain et al, 2020b(Hossain et al, , 2022.…”

“…Recently, transient receptor potential (TRP) channels have been targeted to develop a pharmacological treatment strategy for oropharyngeal dysphagia (Hossain et al, 2020a;Tomsen et al, 2022). We have previously observed that activation of TRP vanilloid 1 (TRPV1), TRP ankyrin 1 (TRPA1), and TRP melastatin 8 (TRPM8) channels, which are present in the peripheral swallowing-related regions, trigger the swallowing reflex (Hossain et al, 2018(Hossain et al, , 2022. Those observations prompted us to examine the involvement of transient receptor potential vanilloid 4 (TRPV4) in triggering the reflex.…”