MUCOSAL DEFENSE AND POSSIBLE INTERFERENCE WITH HEALING

Objective: Gastric mucosal defense and repair are independent phenomen a and involve different mechanisms. The sensory neuronal system is an important mediator of protective effects. The aim of the present study was to investigate whether these neurons are also involved in mucosal repair. Design: Defense against and healing of acute gastric mucosal damage were studied in control rats, in rats after functional ablation of sensory neurons and in rats after inhibition of nitric oxide biosy nthesis. Methods: Functional ablation of sensory neurons was induced b y treatment with a neurotoxic dose of capsaicin. Gastric mucosa was da maged by ethanol. Protection and healing were assessed macroscopically , histologically, and by determination of gastric myeloperoxidase acti vity. Additionally, the protective and healing effects of treatment wi th the nitric oxide biosynthesis inhibitor N(G)-nitro-L-arginine methy l ester (L-NAME) were investigated. Results: Functional ablation of se nsory neurons delayed the healing of mucosal damage and promoted the d evelopment of deep ulcers, predominantly in the antrum region, associa ted with a marked invasion of inflammatory cells and increased gastric myeloperoxidase activity. Treatment with L-NAME abolished the protect ive effect of sensory neuron stimulation but did not mimic the effects of functional sensory neuron ablation on mucosal repair. L-NAME did n ot affect ulceration and inflammation in the mucosa of rats after the functional ablation of sensory neurons. Conclusions: Sensory neurons c ontribute to defense and repair and limit the inflammatory response in injured gastric mucosa. In contrast to the gastroprotection elicited by stimulation of sensory neurons, effects on healing of mucosal damag e are independent of the nitric oxide system.