TRPM8, ASIC1, and ASIC3 localization and expression in the human oropharynx.

BACKGROUND: Oropharyngeal dysphagia (OD) is a prevalent disease with poor prognosis among older people and has no pharmacological treatment. Polymodal sensory receptors like the TRP or ASIC family receptors are potential targets to treat OD. TRPM8 agonists and acidic solutions can improve the swallow response in patients with OD, but little is known about the expression of TRPM8, ASIC1, and ASIC3 in the human oropharynx. The aim of this study was to assess the expression and localization of TRPM8, ASIC1, and ASIC3 in human samples of the oropharynx to lay the basis for new pharmacological treatments for OD. METHODS: Pathology-free samples from oropharyngeal regions innervated by cranial nerves V, IX, and X were obtained during major ENT surgery and processed to obtain mRNA (20 patients) or to be used in immunohistochemical assays (12 patients). TRPM8, ASIC1, and ASIC3 expression and localization were studied with RT-qPCR and fluorescent immunohistochemistry. KEY RESULTS: ASIC3 was expressed in the 3 regions studied with similar levels and was localized on sensory fibers innervating the mucosa below the basal lamina of all studied regions. TRPM8 was also co-localized on the sensory fibers innervating the mucosa below the basal lamina of all studied regions. In contrast, ASIC1 was only found in the nerves innervating the tongue muscular fibers. CONCLUSIONS & INFERENCES: TRPM8 and ASIC3 are found on submucosal sensory nerves in the human oropharynx. Our study lays the basis to use oropharyngeal TRPM8 and ASIC3 receptors as therapeutic targets to develop new active pharmacological treatments for OD patients.

Localization and expression of TRPV1 and TRPA1 in the human oropharynx and larynx.

BACKGROUND: Previous studies have found that TRPV1 and TRPA1 receptor agonists improve swallow response in patients with oropharyngeal dysphagia (OD), but little is known about the expression of these receptors in the human oropharynx. The aim of this study was to assess the expression and localization of TRPV1 and TRPA1 in human samples from the oropharynx of healthy patients, to provide the basis for new pharmacological treatments for OD. METHODS: Samples from oropharyngeal regions innervated by cranial nerves V, IX, and X (tongue, pharynx, and epiglottis) were obtained during ENT surgery and processed either for mRNA (21 patients) or for immunohistochemical assays (seven patients). The expression analysis was performed with RT-qPCR using ACTBh as reference gene. Hemotoxylin and eosin staining was used to study the histology; the immunohistochemical assay used (i) neuron-specific enolase to detect nerve fibers or (ii) fluorescent probes to locate TRPV1 and TRPA1. RESULTS: TRPV1 was expressed in the three studied regions, with higher levels in CN V region (tongue) than in CN X region (epiglottis; p < 0.05), and was localized at epithelial cells and nociceptive fibers in all studied regions. TRPA1 was also expressed in all studied regions, but was always localized below the basal lamina. No immunoreactivity for TRPA1 was found on epithelial cells. CONCLUSIONS & INFERENCES: TRPV1 and TRPA1 are widely expressed in the human oropharynx with two distinct patterns. Our study further confirms that TRPV1/A1 receptors are promising therapeutic targets to develop active treatments for OD patients.

[Efficacy and safety of dotarizine vs. cinnarizine in the symptomatic treatment of acute balance disorders (common vertigo)]. / Eficacia y seguridad de dotarizina frente a cinarizina en el tratamiento sintomático de los trastornos agudos del equilibrio (vértigo común).

One hundred and ten adult patients suffering from peripheral vertigo were treated in a multifactorial double-blind randomized clinical trial with dotarizine (50 mg b.i.d.) or cinnarizine (75 mg b.i.d.). There was a 60 days clinical follow-up. Results showed that dotarizine was significantly active against the vertigo attacks and its associated symptoms (mainly neurovegetative). The global superiority of dotarizine was confirmed by statistically significant differences between treatments in the improvement of the severity of vertigo, hearing loss in audiometries, global relief of symptoms, disability produced by crises and global assessment by the investigators themselves. No clinically significant unwanted effects were seen in either group on blood pressure, heart rate or analytical parameters. No serious adverse effects to dotarizine were reported. This study confirms the value of dotarizine in the treatment of peripheral vertigo.