A comparative study on the therapeutic effect of TRPV1, TRPA1, and TRPM8 agonists on swallowing dysfunction associated with aging and neurological diseases

Abstract

Background: Oropharyngeal sensory impairment is a potential target to treat swallowing dysfunction in patients with oropharyngeal dysphagia (OD).

Aim: To assess the therapeutic effect of stimulating oropharyngeal sensory afferents with TRPV1, TRPA1, or TRPM8 agonists vs increasing bolus viscosity in older and neurologic patients with OD by comparing four studies of similar experimental design.

Methods: Swallow function of 142 older patients with impaired safety of swallow at nectar ([50-350] mPa·s) viscosity was evaluated with videofluoroscopy (VFS) while treated with TRPV1 (150 μmol/L), TRPV1/A1 (150 μmol/L and 1 mmol/L), or TRPM8 (1 mmol/L or 10 mmol/L) agonists or modified starch (MS) at spoon thick viscosity (>1750 mPa·s).

Results: TRPV1 stimulation with capsaicinoids reduced penetrations by 50%, pharyngeal residue by 80%, and LVC time by 24.38% and increased bolus velocity by 36.51%. TRPV1/A1 stimulation with piperine reduced penetrations by 56.32%, LVC time by 25.55% and increased bolus velocity by 23.63%. TRPM8 stimulation with menthol 1 mmol/L reduced penetrations by 37.5% while 10 mmol/L reduced LVC time by 18.44%. Thickeners reduced penetrations by 77.11%, but increased pharyngeal residue by 19.89%, delayed LVC by 41.73%, and reduced bolus velocity by 13.44%.

Conclusion: Natural capsaicinoids have a stronger therapeutic effect on VFS signs and swallow response by stimulating TRPV1 than TRPV1/A1 or TRPM8 agonists. While TRP stimulants increased bolus velocity and reduced swallow response times, thickeners reduced bolus velocity and further delayed the swallow response. This study sets the bases to develop new pharmacologic strategies for older patients with OD, moving away from compensation toward the recovery of swallow function.

Keywords: capsaicin; dysphagia; menthol; piperine; thickeners.