Chemical and Biological Tools for the Study of Voltage-Gated Sodium Channels in Electrogenesis and Nociception

The malfunction and misregulation of voltage-gated sodium channels (Na_V s) underlie in large part the electrical hyperexcitability characteristic of chronic inflammatory and neuropathic pain. Na_V s are responsible for the initiation and propagation of electrical impulses (action potentials) in cells. Tissue and nerve injury alter the expression and localization of multiple Na_V isoforms, including Na_V 1.1, 1.3, and 1.6-1.9, resulting in aberrant action potential firing patterns. To better understand the role of Na_V regulation, localization, and trafficking in electrogenesis and pain pathogenesis, a number of chemical and biological reagents for interrogating Na_V function have been advanced. The development and application of such tools for understanding Na_V physiology are the focus of this review.