Abstract
Oropharyngeal dysphagia, or difficulty in swallowing, is a major health problem that can lead to serious complications, such as pulmonary aspiration, malnutrition, dehydration, and pneumonia. The current clinical management of oropharyngeal dysphagia mainly focuses on compensatory strategies and swallowing exercises/maneuvers; however, studies have suggested their limited effectiveness for recovering swallowing physiology and for promoting neuroplasticity in swallowing-related neuronal networks. Several new and innovative strategies based on neurostimulation in peripheral and cortical swallowing-related regions have been investigated, and appear promising for the management of oropharyngeal dysphagia. The peripheral chemical neurostimulation strategy is one of the innovative strategies, and targets chemosensory ion channels expressed in peripheral swallowing-related regions. A considerable number of animal and human studies, including randomized clinical trials in patients with oropharyngeal dysphagia, have reported improvements in the efficacy, safety, and physiology of swallowing using this strategy. There is also evidence that neuroplasticity is promoted in swallowing-related neuronal networks with this strategy. The targeting of chemosensory ion channels in peripheral swallowing-related regions may therefore be a promising pharmacological treatment strategy for the management of oropharyngeal dysphagia. In this review, we focus on this strategy, including its possible neurophysiological and molecular mechanisms.
Highlights
Swallowing is a physiological process that transports ingested materials and saliva from the oral cavity into the stomach [1,2,3,4,5]
The findings of this study suggest that chronic TRPV1 stimulation in peripheral swallowing-related regions leads to neuroplastic changes in the cerebral cortex that augment any improvements in swallowing function [79]
Evidence from various studies suggests that the activation of chemosensory ion channels in peripheral swallowing-related regions may be a potential strategy for the development of new active pharmacological treatments of oropharyngeal dysphagia
Summary
Swallowing is a physiological process that transports ingested materials (e.g., foods and liquids) and saliva from the oral cavity into the stomach [1,2,3,4,5]. Transcutaneous electrical sensory stimulation to activate the peripheral sensory nerves (without muscle contraction) leads to a reduced swallow response time and frequency of aspiration in patients with oropharyngeal dysphagia after stroke, but not in patients with Parkinson’s disease [104,110,111,112]. In patients with oropharyngeal dysphagia, the activation of these channels by their chemical agonists in peripheral swallowing-related regions results in significant improvements in many of the biomechanical events of swallowing physiology, safety, and efficacy [44,48,49,79,82,113,114,115,118,119] This strategy is promising for the development of pharmacological therapeutics for oropharyngeal dysphagia [36,37]. An understanding of the molecular and neurophysiological mechanisms is important for the development of effective therapeutics
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