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 (NaVs) underlie in large part the electrical hyperexcitability characteristic of chronic inflammatory and neuropathic pain. NaVs 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 NaV isoforms, including NaV1.1, 1.3, and 1.6–1.9, resulting in aberrant action potential firing patterns. To better understand the role of NaV regulation, localization, and trafficking in electrogenesis and pain pathogenesis, a number of chemical and biological reagents for interrogating NaV function have been advanced. The development and application of such tools for understanding NaV physiology are the focus of this review. A desire to understand the role of voltage‐gated sodium channels in electrical signaling and pain perception has motivated the development of chemical and biological tools that target this protein class. Such advances are summarized in this account and future research opportunities are highlighted.