Shigeyuki Mukudai

Objectives: Vocal fold scar remains a therapeutic challenge. Vocal fold fibroblasts (VFFs) secrete extracellular matrix (ECM), and transforming growth factor‐beta 1 (TGF‐β1)‐mediated fibroblast to myofibroblast differentiation is central to the development of fibrosis. The transient receptor potential (TRP) channel superfamily is a group of nonselective cation channels, and activation of TRP ankyrin 1 (TRPA1) channel has been shown to have antifibrotic effects through TGF‐β1/Smad signaling in various organs. This study aimed to elucidate expression of TRPA1 and the impact of TRPA1 activation on TGF‐β1/Smad signaling in VFFs.Methods: Vocal folds were dissected from 10‐week‐old, male Sprague‐Dawley rats and primary VFFs were established. TRPA1 was examined in VFFs and lamina propria via immunostaining. VFFs were treated with allyl isothiocyanate (AITC, TRP channel agonist, 10⁻⁵ M) ± TGF‐β1 (10 ng/ml) ± A‐967079 (selective TRPA1 channel antagonist, 5.0 × 10⁻⁷ M) for 4 or 24 h. Trpa1, Smad3, Smad7, Col1a1, Acta2, and Has1 mRNA expression were quantified via qPCR.Results: TRPA1 was expressed in cultured VFFs and the lamina propria. TGF‐β1 administration significantly increased Trpa1 compared to control. AITC alone did not alter Smad3, Smad7, Acta2, or ECM related genes. However, the combination of AITC and TGF‐β1 significantly increased Smad3 and decreased Smad7 and Acta2 compared to TGF‐β1 alone; A‐967079 significantly reduced this response.Conclusions: VFFs expressed TRPA1, and the activation of TRPA1 regulated TGF‐β1/Smad signaling in VFFs. These findings provide preliminary insights into potential anti‐fibrotic mechanisms of TRPA1 activation through TGF‐β1/Smad signaling in VFFs.Level of Evidence: NA Laryngoscope, 134:4593–4598, 2024

Objectives: To examine the sustained effects of oropharyngeal capsaicin stimulation on the regulation of swallowing, we recorded the swallowing‐related nerve activities during continuous infusion of capsaicin solution into the oropharynx.Methods: In 33 in situ perfused brainstem preparation of rats, we recorded the activities of the vagus, hypoglossal, and phrenic nerves during fictive swallowing. The interburst intervals (IBIs) of the swallowing‐related nerves during sequential pharyngeal swallowing (sPSW) elicited by electrical stimulation of the superior laryngeal nerve (SLN) during concurrent capsaicin stimulation of 10, 1, and 0.1 μM (n = 28) were compared with those during oropharyngeal infusion of saline (control) (n = 5).Results: The IBIs during SLN‐induced sPSW were reduced at 5 min after initiation of continuous infusion of 10 and 1 μM capsaicin solution. The IBIs showed significant decreases to −25.8 ± 6.9%, −25.9 ± 5.3, −18.3 ± 3.7, and −12.0 ± 1.6 at 30 min following 1 μM capsaicin stimulation at SLN stimulus conditions at 5 Hz of 1.2 times threshold, 10 Hz of 40 μA, 5 Hz of 60 μA, and 10 Hz of 60 μA, respectively. Continuous capsaicin stimulation of 0.1 μM solution did not show significant sustained effects.Conclusion: Pharmacological stimulation of capsaicin could provide time‐dependent effects on the likelihood of swallowing, particularly subserving sustained facilitation of swallowing reflex with appropriate concentration of capsaicin.Level of Evidence: NA Laryngoscope, 134:305–314, 2024