Diagnostic and therapeutic use of capsaicin in the GI tract

Our laboratory has previously shown that the polymodal capsaicin receptor VR1 mediates painful and non painful sensations in the upper gastrointestinal tract. Data also suggest that subjects with dyspeptic symptoms are hypersensitive to intraluminally applied capsaicin and that repeated application of capsaicin might desensitize the VR1 receptor and lead to improvement of dyspeptic symptoms in patients with functional dyspepsia. The present protocol is designed to develop a simple diagnostic test by application of capsaicin via a capsule into the gut and to evaluate the possible therapeutic implication of this capsaicin test. HYPOTHESES: (I) Oral application of capsaicin dose dependently induces upper gastrointestinal symptoms, more so in patients with dyspepsia than healthy controls (II) Patients with a decreased tolerance against capsaicin respond to a therapy that desensitizes the VR1 receptor by improving the symptoms, while symptoms of patients with normal capsaicin sensitivity do not respond to chronic capsaicin application. METHODS AND MATERIAL: Healthy subjects as well as patients with functional upper gastrointestinal symptoms will be studied. The diagnostic test will be evaluated in healthy subjects and patients with functional dyspepsia. All patients will be offered to receive capsaicin over a five week period to evaluate the therapeutic effect of repeated capsaicin application. It will be tested whether patients with a sensitivity to capsaicin that is in the normal range respond to the capsaicin treatment differently from those patients with an increased sensitivity. SUMMARY: This study is designed to improve our understanding of the relevance of chemical nociception in the generation of pain arising from the gut and modulation of nociception by capsaicin. It will give new insights into the pathophysiological mechanisms of gastrointestinal pain and into possible new treatment modalities.

The Capsaicin test was developed to determine the sensation thresholds for chemical stimuli in the stomach. In the present project healthy subjects and several groups of patients received a capsaicin test to determine their visceral sensation thresholds: patients studied were patients with functional dyspepsia, chronic inflammatory bowel disease, gastric ulcer and irritable bowel syndrome. Visceral sensation thresholds were significantly higher in healthy volunteers as compared to patients with functional dyspepsia. But even within the group of patients with functional dyspepsia, a subgroup was determined with distinctly reduced sensation threshold while another subgroup existed with the sensation threshold in the normal range. Visceral sensation thresholds in the other groups studied were significantly higher as compared to the functional dyspepsia group and comparable with the healthy control group. Thus chemical hypersensitivity of the stomach (visceral hypersensitivity) affects only patients with functional dyspepsia and might be causally linked to symptoms of functional dyspepsia such as recurring nausea, early satiety, fullness, abdominal distension or epigastric pain. Capsaicin induced symptoms differ in patients with functional dyspepsia and healthy volunteers not only in their severity but also in the quality of the symptoms. The duration of capsaicin induced symptoms was significantly longer in patients with functional dyspepsia than in healthy subjects. While in healthy volunteers a sip of water regularly terminated capsaicin induced symptoms immediately, this is not the case in functional dyspepsia patients. It was also shown that symptoms induced by capsaicin are not related to the psychological profile of the patients. Finally a group of patients with functional dyspepsia was divided in one subgroup with a positive capsaicin test that is a significantly decreased visceral sensation threshold (visceral hypersensitivity) - and one subgroup with the capsaicin test in the normal range. Both groups received low dose capsaicin tid. over four weeks in a therapeutic trial. After 4 weeks both subgroups had significantly less symptoms as compared to the start period of the trial. Moreover, the benefit of the capsaicin therapy was significantly higher in the subgroup of functional dyspepsia that had a positive capsaicin test at the beginning of the trial.