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Brain and Pharyngeal Responses Associated with Pharmacological Treatments for Oropharyngeal Dysphagia in Older Patients

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Abstract

Impaired pharyngo-laryngeal sensory function is a critical mechanism for oropharyngeal dysphagia (OD). Discovery of the TRP family in sensory nerves opens a window for new active treatments for OD. To summarize our experience of the action mechanism and therapeutic effects of pharyngeal sensory stimulation by TRPV1, TRPA1 and TRPM8 agonists in older patients with OD. Summary of our studies on location and expression of TRP in the human oropharynx and larynx, and clinical trials with acute and after 2 weeks of treatment with TRP agonists in older patients with OD. (1) TRP receptors are widely expressed in the human oropharynx and larynx: TRPV1 was localized in epithelial cells and TRPV1, TRPA1 and TRPM8 in sensory fibers mainly below the basal lamina. (2) Older people present a decline in pharyngeal sensory function, more severe in patients with OD associated with delayed swallow response, impaired airway protection and reduced spontaneous swallowing frequency. (3) Acute stimulation with TRP agonists improved the biomechanics and neurophysiology of swallowing in older patients with OD TRPV1 = TRPA1 > TRPM8. (4) After 2 weeks of treatment, TRPV1 agonists induced cortical changes that correlated with improvements in swallowing biomechanics. TRP agonists are well tolerated and do not induce any major adverse events. TRP receptors are widely expressed in the human oropharynx and larynx with specific patterns. Acute oropharyngeal sensory stimulation with TRP agonists improved neurophysiology, biomechanics of swallow response, and safety of swallowing. Subacute stimulation promotes brain plasticity further improving swallow function in older people with OD.

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Modified from Alvarez-Berdugo et al. 2016 and 2018. Parts of this figure were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/)

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Funding

This work has been supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCIII) (PI14/00453 and PI18/00241); Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, ISCIII (EHD16PI02); Proyectos de Investigación Clínica Independiente, ISCIII (ICI20/00117); Programa de Estabilización de Investigadores/Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (INT15/00026 and INT16/00111); Agencia de Gestió d’Ajuts Universitaris i de Recerca (2009 SGR 708 and 2014 SGR 789); Fundació la Marató de TV3 (Project 112310): Agrupació Mutua; and Nestlé Health Science.

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  1. Gastrointestinal Physiology Laboratory, Hospital de Mataró, Consorci Sanitari del Maresme, Mataró, Spain

    Pere Clavé, Omar Ortega, Laia Rofes, Daniel Alvarez-Berdugo & Noemí Tomsen

  2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

    Pere Clavé & Omar Ortega

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  1. Pere Clavé
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  2. Omar Ortega
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  3. Laia Rofes
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  4. Daniel Alvarez-Berdugo
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  5. Noemí Tomsen
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Correspondence to Noemí Tomsen.

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Clavé, P., Ortega, O., Rofes, L. et al. Brain and Pharyngeal Responses Associated with Pharmacological Treatments for Oropharyngeal Dysphagia in Older Patients. Dysphagia 38, 1449–1466 (2023). https://doi.org/10.1007/s00455-023-10578-x

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