Signalling the state of the digestive tract.

The gastrointestinal tract has a rich sensory innervation. Extrinsic afferents in vagal, splanchnic and pelvic nerves project to the CNS where gut reflex function is coordinated and integrated with behavioural responses (e.g. regulation of food intake) and mediate sensations. The afferent information conveyed by vagal and spinal mechanosensitive afferents can be very different. Vagal afferents have low thresholds of activation and reach maximal responses within physiological levels of distension. In contrast, spinal afferents, although many have corresponding thresholds for activation, are able to respond beyond the physiological range and encode both physiological and noxious levels of stimulation. However, mechanosensitivity is not fixed but can be influenced by a wide range of chemical mediators released as a consequence of ischemia, injury and inflammation. Indeed, previously mechanical insensitive afferents can develop mechanosensitivity during inflammation and a variety of chemical mediators are implicated in this sensitisation process. Chemosensitivity is also a property of vagal mucosal afferents that detect the chemical milieu for chemicals absorbed across the epithelium or released from enteroendocrine cells that are strategically positioned to "taste" luminal contents. Thus, there exists a complex interplay between immunomodulators, neurotransmitters and neuroendocrine factors that underlie gastrointestinal sensing mechanisms and enable orchestration of appropriate host responses.