Voltage-gated sodium channels: (NaV)igating the field to determine their contribution to visceral nociception

Abstract

Chronic visceral pain, altered motility and bladder dysfunction are common, yet poorly managed symptoms of functional and inflammatory disorders of the gastrointestinal and urinary tracts. Recently, numerous human channelopathies of the voltage-gated sodium (NaV) channel family have been identified, which induce either painful neuropathies, an insensitivity to pain, or alterations in smooth muscle function. The identification of these disorders, in addition to the recent utilisation of genetically modified NaV mice and specific NaV channel modulators, has shed new light on how NaV channels contribute to the function of neuronal and non-neuronal tissues within the gastrointestinal tract and bladder. Here we review the current pre-clinical and clinical evidence to reveal how the nine NaV channel family members (NaV1.1–NaV1.9) contribute to abdominal visceral function in normal and disease states.