Sensory neurone responses to mucosal noxae in the upper gut: relevance to mucosal integrity and gastrointestinal pain.

The digestive tract is supplied by extrinsic and intrinsic sensory neurones that, together with endocrine and immune cells, form a surveillance network that is essential to gut function. This article focuses on the responses of extrinsic afferent neurones to chemical insults of the gastrointestinal mucosa and their pathophysiological relevance to mucosal integrity and abdominal pain. Within the gastroduodenal region, spinal afferents subserve an emergency function because, in case of alarm by influxing acid, they stimulate mechanisms of mucosal protection via an efferent-like release of transmitters. Other sensory neurones signal chemical noxae to the brain, a task that is not confined to spinal afferents because vagal afferents communicate gastric acid and peripheral immune challenges to the brainstem and in this way elicit autonomic, endocrine, affective and behavioural reactions. Emerging evidence indicates that hypersensitivity of extrinsic afferent pathways to mechanical and chemical stimuli makes an important contribution to the abdominal hyperalgesia seen in functional dyspepsia and irritable bowel syndrome. Sensitization may be brought about by inflammatory processes that lead to up-regulation and functional alterations of receptors and ion channels on sensory neurones. Such sensory neurone-specific molecules, which include vanilloid (capsaicin) receptors, may represent important targets for novel drugs to treat abdominal pain.