ROLE OF CAPSAICIN-SENSITIVE SENSORY NERVES IN GASTROPROTECTION AGAINST ACID-INDEPENDENT AND ACID-DEPENDENT ULCEROGENS

Treatment with small doses of topical capsaicin protects the gastric m ucosa from the damage by strong irritants but functional ablation of s ensory nerves by pretreatment with larger dose of parenteral capsaicin augments the formation of gastric lesions via unknown mechanism. This study was designed to determine the role of gastric acid secretion, m ucosal blood flow (GBF) and prostaglandins (PG) generation in the gast roprotection induced by small doses of topical or parenteral capsaicin in rats with intact or capsaicin-deactivated sensory nerves. Gastric lesions were produced in rats with intact sensory nerves (series A) or capsaicin-deactivated nerves (series B) using intragastric (i.g.) app lication of 100% ethanol, acidified aspirin (ASA) or water immersion a nd restraint stress (WRS). Pretreatment with i.g. capsaicin (0.12-1.0 mg/kg) in rats with intact sensory nerves (series A) reduced dose-depe ndently the mucosal damage caused by ethanol, ASA or WRS, the dose inh ibiting the lesion area by 50% (ID50) being 0.3, 0.5 and 0.7 mg/kg, re spectively. This protection was accompanied by a significant rise in g astric mucosal blood flow (GBF). Parenteral application of capsaicin ( 1.2-10 mg/kg s.c.) that in intact rats dose-dependently increased GBF, also dose-dependently reduced gastric damage induced by ASA or WRS (b ut not by ethanol), the ID50 being 5 and 3 mg/kg, respectively. The re duction by i.g. capsaicin of ethanol- or WRS-induced mucosal lesions w as accompanied by a rise in GBF and this effect was reversed by indome thacin at a dose that suppressed endogenous PG biosynthesis by about 9 0%, indicating that PG are involved in the protective activities of to pical capsaicin. Furthermore, topical and to a lesser extent parentera l capsaicin given to rats with intact or deactivated sensory nerves in hibited gastric acid and pepsin outputs, suggesting that this inhibiti on could contribute to the capsaicin-induced gastroprotection against acid-dependent mucosal lesions (ASA or WRS). Capsaicin deactivation of sensory nerves aggravated mucosal lesions induced by all three ulcero gens and this effect was accompanied by a marked decrease in GBF. In s uch capsaicin-deactivated rats, topical capsaicin also reduced ethanol -, ASA- or WRS-induced lesions, while parenteral capsaicin was effecti ve only in the protection against the damage induced by acidified ASA and WRS but not by ethanol. The protection against WRS lesions and acc ompanying rise in GBF by parenteral capsaicin were also reversed by th e pretreatment with indomethacin applied in a dose suppressing the gen eration of PG. We conclude that capsaicin is capable of protecting gas tric mucosa in rats with both intact and capsaicin-deactivated rats an d that this protective activity depends, at least in part, upon its hy peremic and antisecretory effects that may be mediated, at least in pa rt, by endogenous release of PG.