Localization and expression of <scp>TRPV</scp>1 and <scp>TRPA</scp>1 in the human oropharynx and larynx

Álvarez-Berdugo, Daniel; Rofes, Laia; Farré, Ricard; Casamitjana, J. Francesc; Enrique, Adrián; Chamizo, J.; Padrón, Andreína; Navarro, Xavier; Clavé, Père

doi:10.1111/nmo.12701

Cited by 68 publications

(49 citation statements)

References 49 publications

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“…It is known that free nerve endings penetrate the epithelium in the skin, but there is little evidence about their presence within the oropharyngeal epithelium. The evidence collected in our review and many of our experiments on human tissue indicate a dense submucosal innervation in contrast to scarce cases of intraepithelial fibers (Fig. S1).…”

Section: Discussionmentioning

confidence: 68%

“…In the oral cavity and oropharynx, TRPV1 has been detected at both the mRNA and protein levels in the tongue mucosa in nerve terminals and epithelial cells; immunoreactivity to TRPV1 has also been found in nerve fibers innervating the human larynx . A recent study also found TRPV1 expression in the mucosa of the human tongue, pharynx, and epiglottis and TRPV1 immunoreactivity on the membranes of epithelial cells of these regions, as well as on nerve fibers and leukocytes (Fig. S3).…”

Section: Receptors For Chemosensation and Thermosensationmentioning

confidence: 70%

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Oropharyngeal and laryngeal sensory innervation in the pathophysiology of swallowing disorders and sensory stimulation treatments

Álvarez-Berdugo

Rofes

Casamitjana

et al. 2016

Annals of the New York Academy of Sciences

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Oropharyngeal dysphagia (OD) affects older and neurological patients, causing malnutrition and dehydration and increasing the risk for aspiration pneumonia. There is evidence that sensory deficits in those populations are closely related to swallowing disorders, and several research groups are developing new therapies based on sensory stimulation of this area. More information on the sensory innervation participating in the swallow response is needed to better understand the pathophysiology of OD and to develop new treatments. This review focuses on the sensory innervation of the human oropharynx and larynx in healthy people compared with patients with swallowing disorders in order to unravel the abnormalities that may lead to the loss of sensitivity in patients with OD. We also hypothesize the pathway through which active sensory-enhancement treatments may elicit their therapeutic effect on patients with swallowing dysfunctions. As far as we know, this is the first time a review covers the anatomy, histology, ultrastructure, and molecular biology of the sensory innervation of the swallowing function.

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Section: Discussionmentioning

confidence: 68%

Section: Receptors For Chemosensation and Thermosensationmentioning

confidence: 70%

Oropharyngeal and laryngeal sensory innervation in the pathophysiology of swallowing disorders and sensory stimulation treatments

Álvarez-Berdugo

Rofes

Casamitjana

et al. 2016

Annals of the New York Academy of Sciences

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“…All of these studies included groups of patients with poststroke OD, where these agonists showed significant effects on VFS signs of swallow response. We also recently studied the expression of TRPV1/A1 receptors in the human oropharynx, further confirming that these receptors are promising therapeutic targets to develop active treatments for OD patients …”

Section: Advances In Treatmentmentioning

confidence: 64%

“…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 . Preliminary studies from our group show that the cortical activation of stroke patients with OD in response to pharyngeal electrical stimulus is delayed compared with healthy volunteers.…”

Section: Advances In the Pathophysiology Of Poststroke Odmentioning

confidence: 80%

Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function

Cabib

Ortega

Kumru

et al. 2016

Annals of the New York Academy of Sciences

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Oropharyngeal dysphagia (OD) is very prevalent among poststroke patients, causing severe complications but lacking specific neurorehabilitation treatment. This review covers advances in the pathophysiology, diagnosis, and physiologically based neurorehabilitation strategies for poststroke OD. The pathophysiology of oropharyngeal biomechanics can be assessed by videofluoroscopy, as delayed laryngeal vestibule closure is closely associated with aspiration. Stroke may affect afferent or efferent neuronal circuits participating in deglutition. The integrity of oropharyngeal-cortical afferent pathways can be assessed by electroencephalography through sensory-evoked potentials by pharyngeal electrical stimulation, while corticopharyngeal efferent pathways can be characterized by electromyography through motor-evoked potentials by transcranial magnetic stimulation. Dysfunction in both cortico-mediated evoked responses is associated with delayed swallow response and aspiration. Studies have reported hemispherical asymmetry on motor control of swallowing and the relevance of impaired oropharyngeal sensitivity on aspiration. Advances in treatment include improvements in compensatory strategies but are mainly focused on (1) peripheral stimulation strategies and (2) central, noninvasive stimulation strategies with evidence of their clinical benefits. Characterization of poststroke OD is evolving from the assessment of impaired biomechanics to the sensorimotor integration processes involved in deglutition. Treatment is also changing from compensatory strategies to promoting brain plasticity, both to recover swallow function and to improve brain-related swallowing dysfunction.

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“…SP is released by activation of transient receptor potential vanilloid 1 (TRPV1), which is expressed in the oral mucosa, gastrointestinal (GI) tract mucosa, and airway mucosa [20]. TRPV1 is considered to be a therapeutic target of OD [21]. Capsaicin is a specific agonist to TRPV1, and it has occasionally been reported that administration of capsaicin improves OD [22,23,24,25].…”

Section: Introductionmentioning

confidence: 99%

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study

Nakato¹,

Manabe²,

Shimizu

et al. 2017

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Background/Aims: The standard of care for older patients with oropharyngeal dysphagia (OD) is poor. Stimulation of transient receptor potential vanilloid 1 might become a pharmacological strategy for these patients. This study aimed to compare the therapeutic effect of film food containing 0.75 µg of capsaicin in these patients. Methods: In a crossover, randomized trial, 49 patients with OD were provided capsaicin or identical placebo at least 7 days apart. Patients' reported symptoms during repeated swallowing, the volume, pH and substance P (SP) concentrations in saliva, and cervical esophageal wall motion evaluated by ultrasonographic tissue Doppler imaging were obtained before and after capsaicin or placebo administration. Results: Significantly more patients with OD who took capsaicin experienced improvement in symptoms than those who took placebo. Salivary SP levels were significantly increased after capsaicin administration compared with placebo in the effective group. The duration of cervical esophageal wall opening was significantly shorter in capsaicin administration in the effective group. Furthermore, a significant negative correlation was found between the duration of cervical esophageal wall opening and salivary SP levels. Conclusion: Elevated salivary SP concentrations stimulated by capsaicin greatly improve the safety and efficacy of swallowing, and shorten the swallow response in older patients with OD.

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

Abstract: 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.

Cited by 68 publications

References 49 publications

Oropharyngeal and laryngeal sensory innervation in the pathophysiology of swallowing disorders and sensory stimulation treatments

Oropharyngeal and laryngeal sensory innervation in the pathophysiology of swallowing disorders and sensory stimulation treatments

Neurorehabilitation strategies for poststroke oropharyngeal dysphagia: from compensation to the recovery of swallowing function

Effects of Capsaicin on Older Patients with Oropharyngeal Dysphagia: A Double-Blind, Placebo-Controlled, Crossover Study

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