The experimental use of capsaicin has made possible the discovery that chemosensitive neurons participate in the activation of endogenous mechanisms of protection in the face of pending injury to the gastric mucosa. At present, the pathophysiological potential of this neural emergency system is best reflected by the gastric hyperemic response to acid back-diffusion, a response which is signalled to a large degree by peptidergic afferent neurons. There is good evidence that CGRP released from perivascular afferent nerve endings is an important mediator of the acid-induced hyperemia in the rat gastric mucosa. The vasodilator action of CGRP depends on the formation of NO which functions as a second intercellular messenger of the CGRP-induced vasodilatation. The resulting hyperemia acts to limit acid damage to the superficial part of the mucosa. The hyperemic and protective roles of peptidergic sensory neurons have been studied in most detail in the stomach but there is evidence that they play a similar role in the esophagus, duodenum and colon. Further elucidation of this neural emergency system in the digestive system represents an important area for studies into the pathophysiology and management of gastrointestinal mucosal damage.