Effects of menthol on esophageal motility in humans: Studies using high-resolution manometry

Background/aim: The cold receptor, transient receptor potential melastatin 8 (TRPM8), has been reported to be expressed in esophageal vagal afferents. Esophageal infusion of menthol modulates esophageal perception in reflux patients via TRPM8, but the effects of menthol on esophageal motility are not well investigated. This study aimed to test the hypothesis whether the infusion of menthol into the esophagus could affect esophageal peristaltic characteristics. Methods: Eighteen healthy adults (men 13, mean age 27) underwent high-resolution manometry (HRM) using a catheter with the injection port located in mid-esophagus. Primary peristalsis was performed with ten wet swallows, while secondary peristalsis was generated by 10 rapid air injections. Two different sessions were randomly performed including acute administration of menthol (3 mM) and the placebo. Results: Menthol significantly decreased upper esophageal (UES) pressure of primary peristalsis than the placebo (p = 0.019). There was no difference in distal contractile integral (p = 0.33), distal latency (p = 0.86), basal lower esophageal sphincter pressure (p = 0.19), or 4-second integrated relaxation pressure (p = 0.75) between menthol and placebo. Menthol significantly decreased the frequency of secondary peristalsis subsequent to the administration of menthol during rapid injections with 20 mL air (p = 0.04). Conclusions: Intraluminal infusion of menthol reduces UES basal pressure and inhibits peristaltic frequency of secondary peristalsis. The data suggest that the triggering of secondary peristalsis is probably modulated by TRPM8-sensitive mechanoreceptors; however, the activation of TRPM8 from menthol does not alter esophageal motility following deglutition or distension-induced secondary peristalsis.