Sodium channels and pain: from toxins to therapies

Voltage-gated sodium channels (Na-V channels) are essential for the initiation and propagation of action potentials that critically influence our ability to respond to a diverse range of stimuli. Physiological and pharmacological studies have linked abnormal function of Na-V channels to many human disorders, including chronic neuropathic pain. These findings, along with the description of the functional properties and expression pattern of Na-V channel subtypes, are helping to uncover subtype specific roles in acute and chronic pain and revealing potential opportunities to target these with selective inhibitors. High-throughput screens and automated electrophysiology platforms have identified natural toxins as a promising group of molecules for the development of target-specific analgesics. In this review, the role of toxins in defining the contribution of Na-V channels in acute and chronic pain states and their potential to be used as analgesic therapies are discussed.