Acute effects of capsaicin on gastrointestinal vagal afferents

Capsaicin is an important tool for investigation of thin afferent fibres, but its acute effects on subtypes of vagal afferent endings are unknown. In the gastrointestinal tract, these subtypes are: muscle endings (thought to be purely tension sensitive), mucosal endings (sensitive to stroking and chemical stimuli) and endings in the oesophagus with both properties. Acute capsaicin sensitivity was investigated in ferrets using in vivo and in vitro methods. Single-fibre activity was recorded from 63 vagal afferents: 12 Adelta-fibres, 15 C-fibres and 36 unclassified fibres with endings in the oesophagus (n=42), stomach (n=19) and duodenum (n=2). Responses to capsaicin occurred independently of motility changes and were therefore due to direct activation of the receptor ending. In the oesophagus in vivo, two of 10 tension receptors and one of one mucosal receptor responded to intraluminal application of 3.25 mM capsaicin. In the stomach and duodenum, five of 14 tension receptors and two of four mucosal receptors responded to close-systemic (32-164 nmol) capsaicin. In an in vitro gastro-oesophageal preparation, three of five tension, four of 21 mucosal and two of eight tension/mucosal receptors responded to topical application of 1mM capsaicin. Occurrence of responses was therefore unrelated to location of endings and isolation of tissue. Responsiveness was also unrelated to conduction velocity. Capsaicin caused desensitization of responses to further capsaicin application in 37% of afferents. It additionally caused cross-desensitization to mechanical stimuli, which was also seen in afferents that did not respond directly to capsaicin. In conclusion, capsaicin acutely activates all subtypes of gut vagal afferents in vivo and in vitro, although responsiveness is restricted to 30% of fibres and follows no specific pattern. Acute desensitization may be induced with or without a response.