Chemically Induced Perception in the Duodenum and Jejunum

In an ongoing study we have shown that jejunal perfusion with capsaicin causes upper abdominal sensation in a dose dependent manner and that this sensation is not mediated by mechanoreceptors. We have proposed that chemically induced jejunal perception by capsaicin is brought about via stimulation of the capsaicin receptor VR1, a polymodal receptor that is also activated by acid, noxious heat and ethanol. The present protocol is designed to further assess the role of chemonociception and the VR1 receptor in chemonociception in the upper small intestine and to identify the mechanisms of painful and non-painful chemical sensations in the human gut. AIMS: To demonstrate, that mechanisms, that are known to sensitize the VR1 receptor in vitro, can also sensitize the small intestine in vivo against chemical stimulants but not against mechanical distension. HYPOTHESES: (I) Sensitization of the VR1 receptor in the small intestine will elicit symptoms more promptly and at lower capsaicin doses compared to control perfusions without sensitization. (II) The mechanisms of VR1 receptor sensitization will leave mechanical nociceptors unaltered. METHODS: Studies will be performed in fasting healthy subjects (n= 144). After the volunteers have swallowed a tube assembly, and the infusion site is either in the duodenum or in the jejunum, pressure-controlled balloon distension will be performed. Intestinal distension and capsaicin administration will be performed during infusion of either normal saline, acidic solutions, ethanol (5% vol/vol), or a lipid solution. The capsaicin concentration used will be 20myg/ml (2.5 ml/min). DATA ANALYSIS: Symptom assessment: Subjects will receive a questionnaire evaluating the intensity and type of the symptoms they might experience. The questionnaire will be fully explained to the participants in a standard manner before the study. SUMMARY: This study is designed to improve our understanding of the mechanisms of chemical nociception in the generation of pain arising from the gut and modulation of nociception by interacting stimuli. It will give new insights into the pathophysiological mechanisms of gastrointestinal pain and into possible new treatment modalities.

In an ongoing study we have shown that jejunal perfusion with capsaicin causes upper abdominal sensation in a dose dependent manner and that this sensation is not mediated by mechanoreceptors. We have proposed that chemically induced jejunal perception by capsaicin is brought about via stimulation of the capsaicin receptor VR1, a polymodal receptor that is also activated by acid, noxious heat and ethanol. The present protocol is designed to further assess the role of chemonociception and the VR1 receptor in chemonociception in the upper small intestine and to identify the mechanisms of painful and non-painful chemical sensations in the human gut. AIMS: To demonstrate, that mechanisms, that are known to sensitize the VR1 receptor in vitro, can also sensitize the small intestine in vivo against chemical stimulants but not against mechanical distension. HYPOTHESES: (I) Sensitization of the VR1 receptor in the small intestine will elicit symptoms more promptly and at lower capsaicin doses compared to control perfusions without sensitization. (II) The mechanisms of VR1 receptor sensitization will leave mechanical nociceptors unaltered. METHODS: Studies will be performed in fasting healthy subjects (n= 144). After the volunteers have swallowed a tube assembly, and the infusion site is either in the duodenum or in the jejunum, pressure-controlled balloon distension will be performed. Intestinal distension and capsaicin administration will be performed during infusion of either normal saline, acidic solutions, ethanol (5% vol/vol), or a lipid solution. The capsaicin concentration used will be 20myg/ml (2.5 ml/min). DATA ANALYSIS: Symptom assessment: Subjects will receive a questionnaire evaluating the intensity and type of the symptoms they might experience. The questionnaire will be fully explained to the participants in a standard manner before the study. SUMMARY: This study is designed to improve our understanding of the mechanisms of chemical nociception in the generation of pain arising from the gut and modulation of nociception by interacting stimuli. It will give new insights into the pathophysiological mechanisms of gastrointestinal pain and into possible new treatment modalities.