Role of ion channels in mechanisms controlling gastrointestinal pain pathways.

Hypersensitivity or sensitization of nociceptive primary afferents in the gastrointestinal tract has been proposed as a mechanism for organic and functional gastrointestinal pain. This hypersensitivity can be the result of alterations, either induced by a sensitizing agent or without a peripheral cause, in the functional properties of ion channels located in primary afferents. The tetrodotoxin-resistent sodium channel, known as Na(v)1.8, is present in nociceptive primary afferents, including those from the gut, and it has been implicated as being the main candidate for the enhanced activity that characterizes nociceptor sensitization. Other voltage-gated channels, such as calcium and potassium channels, can also contribute to the sensitization of primary afferents observed in gastrointestinal pain states.