P. HOLZER AFFERENT SIGNALLING OF GASTRIC ACID CHALLENGE Department of Experimental and Clinical Pharmacology, Medical University of Graz, Austria Gastric acid is a factor in the pain associated with peptic ulcer and other acid-related disorders

Gastric acid is a factor in the pain associated with peptic ulcer and other acid-related disorders including functional dyspepsia, given that antisecretory treatment is a mainstay in the treatment of upper abdominal pain. However, the molecular sensors, afferent pathways and central processing systems of gastric chemonociception are little known. This article reviews emerging evidence that vagal afferent pathways play a pivotal role in gastric chemonociception. Exposure of the rat gastric mucosa to backdiffusing concentrations of luminal acid is signalled to the brainstem, but not spinal cord, as visualized by functional neuroanatomy based on the rapid expression of c-fos. This observation is complemented by the finding that the visceromotor response to gastric acid challenge is suppressed by vagotomy, but not splanchnectomy. The gastric acid-induced expression of c-fos in the brainstem is reduced by inhibition of gastric acid secretion and enhanced by pentagastrin-evoked stimulation of gastric acid secretion. These data indicate that endogenous acid modulates the sensory gain of acid-sensitive vagal afferents. Further consistent with a role of these neurons in gastric nociception is the finding that exposure to proinflammatory cytokines and the induction of experimental gastritis or gastric ulceration sensitizes vagal afferent pathways to gastric acid. Taken together, these observations are of relevance to the understanding and treatment of gastric hyperalgesia and dyspeptic pain.