Modification of aspirin and ethanol-induced mucosal damage in rats by intragastric application of resiniferatoxin

The capsaicin analogue ‘resiniferatoxin’ (RTX) was used to investigate the role of capsaicin-sensitive sensory nerves in gastric mucosal injury caused by intragastric (ig) acidified aspirin (200 mg/kg in 2 ml of 0.15 N HCl) or ethanol (2 ml of 50% v/v or 96%) in pylorus-ligated rats. Animals were sacrificed 1, 2 and 4 h later, when gastric secretory responses, number and severity of mucosal lesions were calculated. Intragastric RTX (0.6–1.8 µg/kg) prevented mucosal injury in a dose-dependent manner induced by topical acidified aspirin. The protective effect lasted for 1h and was accompanied by inhibition of gastric acid secretion by RTX. RTX (0.6 and 1.0 µg/kg) co-administered with ethanol reduced mucosal injury caused by 50% ethanol; the protective effect of RTX being more apparent when the drug was given 15 min prior to 50% ethanol. Unexpectedly, RTX co-administered with absolute ethanol aggravated the ethanol-induced mucosal damage. It is concluded that capsaicin-sensitive sensory nerves mediated microcirculatory changes in gastroprotection and these involve inhibition of gastric acid secretion.