Capsaicin effects on stress pathology and gastric acid secretion in rats

Abstract

The effects of capsaicin on stress ulcer formation, plasma corticosterone levels and gastric acid secretion were examined in rats. Capsaicin desensitization did not affect restraint stress ulcer formation but was associated with markedly elevated corticosterone levels, even in non-stressed rats. Acute, orally administered capsaicin augmented ulcer formation only if its administration was followed immediately by restraint stress. Delays of 1,2, or 3 h between drug administration and stress produced ulceration comparable to control values. Capsaicin did not affect basal (non-stimulated) gastric acid secretion but substantially decreased pentagastrin-stimulated acid output. Capsaicin is a major pungent ingredient in a variety of red peppers (species capsicum used as spices in many countries. Capsaicin has been implicated as an etiologic factor in gastrointestinal disease, especially in countries where its use is prevalent (1), however, relatively few studies have examined how capsaicin affects gastrointestinal physiology and pathology. Acute, orally administered capsaicin has been associated with erosive gastritis in rats which could be prevented by pretreatment with histamine H 2 receptor antagonists (2). These data suggested that capsaicin influences histamine-mediated processes in the gut, rather than exerting a direct cytotoxic effect on the mucosal surface. Further evidence favoring this hypothesis was provided by Limlowwongse et al. (1) who showed that oral capsaicin increased gastric acid output in a dose-related fashion in anaeshetized rats. Both hexamethonium and atropine abolished this effect, suggesting that capsaicin may act by influencing cholinergic (vagal) activity associated with the gut. More recently, Szolcsanyi and Bartho (3) proposed that capsaicin exerts a dual action in the stomach. Acute, orally administered, low doses of capsaicin were found to protect rats against development of pyloric-ligation-induced ulcers. However, chronic subcutaneous administration of capsaicin, which produces desensitization (4), and which itself produced no gastric damage, was found to exacerbate subsequent pyloric-ligation-induced ulcers. The authors suggested that acute capsaicin treatment facilitates the release of substances from sensory nerve endings (substance P) which would enhance mucosal blood flow and buffer excess gastric secretion. A chronic, desensitizing regimen of capsaicin, however, would result in diminsshed release from these sensory nerve endings, reduce the extent of gastric vasodilation, and augment ulcer formation. Other studies examining capsaicin effects on the stomach, and in particular, studies employing more physiological models of gastric function are rare. The physiological relevance of studying anaesthetized rats and pyloric-ligation-induced gastric damage has been questioned (5,6) but this model is useful for examining gastric secretory function. However, one useful experimental model is that of stress ulcer, which has emerged as a new diagnostic category over the last decade and which is particularly relevant to human stress ulcer disease (6,7). These ulcers are especially common in infants, the elderly, and among patients in intensive care units following severe trauma, septic shock, burns, and intracranial disease or traumatic head injury. They are characterized by upper gastrointestinal bleeding which can result in a mortality rate of approximately fifty percent (7). Stress ulcers can be reliably produced in animals and such models are essential for understanding the pathogenesis of this disease. Restraint or immobilization is a simple, effective and reproducible animal model of stress ulcer (8,9) and is associated with a reliably high incidence of histologically verifiable ulcers (penetrating the muscularis ) (8) and which respond to current therapeutic regimens, for example, histamine H 2 receptor blockade (10). A second relevant and widely used animal model of gastric function is the chronic gastric cannula preparation (11). In this method, chronic, indwelling gastric cannulae are implanted in the rat forestomach and following a recovery period, conscious gastric acid secretion can be repeatedly sampled from the animals without contaminating effects from anaesthetics or surgery. Accordingly, in the present study, we examined (1) the effects of capsaicin on conscious gastric acid secretion in chronic gastric cannula rats and (2) the effects of capsaicin on stress ulcer and stress pathology in rats.