Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Gastroenterology & Hepatology, 1103 Clinical Sciences, 1109 Neurosciences, 1114 Paediatrics and Reproductive Medicine, 3202 Clinical sciences, 3210 Nutrition and dietetics

Abstract:

Heartburn is the most typical symptom in gastro-esophageal reflux disease (GERD). It has been suggested that heartburn sensation is mediated by the transient receptor potential vanilloid receptor 1 (TRPV1), a cation channel expressed by sensory neurons and activated by heat, acid pH, capsaicin, lipoxygenase products and anandamide. Exposure of the TRPV1 receptor to the agonist capsaicin, the pungent ingredient of chilli peppers, is characterized by activation, followed by receptor desensitization. The aim of the present study was to investigate the effect of intra-esophageal capsaicin instillation on esophageal symptom perception (activation) and on sensitivity to esophageal acid perfusion (desensitization). Methods: Ten healthy volunteers (4m, mean age 271) were studied on three separate occasions, at least one week apart. During standard esophageal manometry, a 10 ml solution of saline containing 0 (placebo), 0.5 (low dose) or 3 (high dose) ml of a capsaicin solution (0.17 mg/ml) were instilled in the mid-esophagus. Thirty minutes later, 0.1 N hydrochloric acid was infused in the middle third of the esophagus at a rate of 6 ml/min for 30 min. At 5-minute intervals, throughout the study, the intensity of 10 symptoms (discomfort, pain, retrosternal burning, epigastric burning, fullness, bloating, nausea, belching, satiety, cramps) was assessed on 10 cm visual analog (VAS) scales. Areas under the curve (AUC) for symptom intensities under different conditions were recorded and compared by paired t-test and ANOVA. Results: Instillation of the high dose of capsaicin induced significantly higher symptoms of retrosternal burning and epigastric burning (AUC 20361 and 15552 mm*min respectively) compared to the low dose (1811 and 3524 mm*min, p< /0.05) and to placebo (6540 and 5343 mm*min, p< /0.05). High dose of capsaicin also induced more pain (AUC 5529 vs. 1515, p< /0.05) and discomfort (AUC 13863 vs. 3330, p=0.05) compared to placebo. During acid perfusion, regardless of the time interval of assessment, capsaicin pretreatment did not significantly alter perception scores for retrosternal burning (AUC 1015254, 1113217 and 890243 respectively for placebo, low dose and high dose, NS), epigastric burning (AUC 740265, 390239 and 408207 respectively for placebo, low dose and high dose, NS), or any other symptom. Conclusion: Instillation of the TRPV1 receptor agonist capsaicin in the esophagus induces symptoms of heartburn and epigastric burning in a dose-dependent fashion. However, as the doses used do not desensitize the esophagus to acid perfusion, identification of the receptor involved in esophageal acid sensitivity awaits other approaches.