Sodium channels and pain: from toxins to therapies.

Voltage-gated sodium channels (NaV 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 NaV channels to many human disorders, including chronic neuropathic pain. These findings, along with the description of the functional properties and expression pattern of NaV 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 NaV channels in acute and chronic pain states and their potential to be used as analgesic therapies are discussed. LINKED ARTICLES: This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc.