The Potential Role for Impaired Mucosal Integrity in the Generation of Esophageal Pain Using Capsaicin in Humans: An Explorative Study

Clin Transl Gastroenterol. 2022 May 1;13(5):e00488. doi: 10.14309/ctg.0000000000000488.


Introduction: Esophageal pain is mediated by sensory nerves, most importantly by the activation of the transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor. TRPV1 is activated and sensitized by a broad range of pungent compounds, as well as inflammatory mediators and tissue irritants. Luminal stressors are suggested to impair the barrier function, which results in consequent activation of these sensory nerve terminals and pain. In this study, we investigated the effect of the perfusion of capsaicin, a TRPV1 agonist, on mucosal impedance and pain in asymptomatic volunteers.

Methods: Thirteen asymptomatic volunteers completed a single-blind, saline-controlled, randomized crossover study. Capsaicin or saline was perfused for 30 minutes in the distal esophagus. Visual analog scale pain intensity scores and intraluminal impedance indicating mucosal integrity were determined. Distal and proximal biopsies were obtained 10 minutes later to measure TRPV1 messenger RNA and TRPV1 immunopositivity, as well as the intercellular space area.

Results: Capsaicin perfusion resulted in significantly greater pain intensity (P = 0.047) and impaired recovery of the mucosal impedance compared with saline-treated controls (P = 0.027). Pain response was significantly associated with decreased mucosal impedance. Similar dynamics were seen in the proximal esophagus, but mucosal impedance recovered entirely to the preinfusion values there. There was a significant association between mucosal impedance and intercellular space width in the distal esophagus. TRPV1 transcription and expression were not significantly altered within this observation period.

Discussion: Esophageal capsaicin perfusion results in pain, which is likely to be explained by impaired mucosal impedance and defective restoration capacity in the distal esophagus.

Trial registration: NCT02603783.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsaicin* / metabolism
  • Cross-Over Studies
  • Humans
  • Mucous Membrane* / innervation
  • Mucous Membrane* / metabolism
  • Pain / etiology
  • Pain / metabolism
  • Single-Blind Method


  • Capsaicin

Associated data