Duodenal chemosensitivity and mechanosensitivity in humans during acid and ethanol perfusion.
BACKGROUND
Chemical stimulation with capsaicin in the intestinal lumen induces abdominal pain, presumably through a mechanism involving the polymodal vanilloid receptor TRPV1 (transient receptor potential vanilloid receptor subtype 1). Other stimulators of TRPV1 include heat, acid or ethanol. We evaluated the effects of duodenal acid and ethanol exposure on chemosensitivity and mechanosensitivity in healthy volunteers.


METHODS
In two placebo-controlled arms of the study, healthy volunteers received duodenal infusions of either hydrochloric acid (0.1 mol/l) (n=8) or ethanol (5% vol/vol) through an oroduodenal tube. Mechanosensitivity was tested applying pressure-controlled duodenal distensions and chemosensitivity was tested by duodenal perfusion with capsaicin (40 microg/ml; 2.5 ml/min). Quality and intensity of upper abdominal symptoms were evaluated with a graded questionnaire during mechanical and chemical stimulation of the duodenum.


RESULTS
During hydrochloric acid infusion, capsaicin-induced perception was reduced (P<0.01) and latency to discomfort was increased from 24.5 min (25th/75th%:16.5/36 min) during placebo to 50 min (25.5/60 min) (P<0.01). Ethanol had no significant effect on chemosensitivity [latency to discomfort for placebo vs. ethanol: 26 min (18/40 min) vs. 20 min (9/60 min)] (P>0.05). Neither duodenal acidification nor ethanol altered mechanosensitivity significantly (P>0.05).


CONCLUSIONS
Duodenal acid activated mechanisms that lead to a decreased sensitivity for intraluminal capsaicin; these mechanisms might protect duodenal chemonociceptors from being sensitized by acid. Whether this mechanism is impaired in patients with upper gastrointestinal functional disease remains to be determined.
Führer
Martina
M
Department of Gastroenterology and Hepatology, Medical University of Vienna, Austria.
Hammer
Johann
J
D000328:Adult; D002211:Capsaicin / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation / Q000379:methods; D011312:Pressure; D011930:Reaction Time / Q000187:drug effects; D012684:Sensory Thresholds / Q000187:drug effects; D016037:Single-Blind Method; D050916:TRPV Cation Channels; D055815:Young Adult
D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D000431:Ethanol; D006851:Hydrochloric Acid; D002211:Capsaicin