Voltage-gated sodium channels and pain

Voltage-gated sodium channels are highly specialized molecular transducers that play a significant role in the creation and transmission of electrical activity throughout the neuraxis. These ion channels are fundamentally involved in sensory neuron physiology and pathophysiology; a complete but localized suspension of their normal function can prevent all sensation--including that perceived as pain. Soft-tissue injuries that result in inflammation or direct damage to nerve fibers have each been shown to result in abnormal sodium channel function and, in many cases, to lead to pathological hyperexcitability in the sensory afferent nerves that innervate the injured dermatome or visceral organ. Abrogating abnormal activity whilst leaving normal sensation unaffected would represent a powerful approach to pain relief. This article reviews the evidence supporting abnormal sodium channel biology in various pathological contexts, the opportunities that this presents for novel therapeutics and progress towards realizing this goal.