ABSTRACT
The maintenance of gastric mucosal integrity depends on the rapid alarm of protective mechanisms in the face of pending injury. Afferent neurons of extrinsic origin constitute an emergency system that is called into operation when the gastric mucosa is endangered by noxious chemicals. The function of these chemoceptive afferents can selectively be manipulated and explored with the excitotoxin capsaicin. Since most of the homeostatic actions of capsaicin-sensitive afferents are brought about by peptides released from their peripheral endings in the gastric wall, the roles of these neurons are described as “sensory-efferent”, “sensory-motor”, “local effector” or “noceffector” to emphasise the functional similarity with the roles of autonomic efferents. When stimulated, chemoceptive afferents enhance gastric blood flow and activate hyperaemia-dependent and hyperaemia-independent mechanisms of protection and repair. Furthermore, they can influence the gastric secretion of acid, bicarbonate and mucus and modulate gastric motility and emptying. In the rodent stomach, the noceffector roles of sensory neurons are mediated by calcitonin gene-related peptide acting via CGRP1 receptors and neurokinin A acting via NK2 receptors, both peptides using nitric oxide as their second messenger. In addition, capsaicin-sensitive neurons form the afferent arc of autonomic reflexes that control secretory and motor functions of the stomach. The pathophysiological potential of the neural emergency system is best portrayed by the gastric hyperaemic response to acid backdiffusion, which is signalled by afferent nerve fibres. This mechanism limits damage to the surface of the mucosa and creates favourable conditions for rapid restitution and healing of the wounded mucosa.
KEY WORDS: stomach; afferent neurons; capsaicin; calcitonin gene-related peptide; tachykinins; substance P; neurokinin A; nitric oxide; gastric blood flow; gastric secretion; gastric motor activity; peptic ulcer disease; ileus.
