Analgesic potential of voltage gated sodium channel modulators for the management of pain

Neuronal electrochemical signals involve the flux of sodium ions through voltage-gated sodium channels (Na_V) located in the neurolemma. Of the nine sodium channel subtypes, Na_V-1.7, 1.8, and 1.9 are predominantly located on nociceptors, making them prime targets to control pain. This review highlights some of the latest discoveries targeting Na_V channel activity, including: (1) charged local anaesthetic derivatives; (2) Na_V channel toxins and associated small peptide blockers; (3) regulation of Na_V channel accessory proteins; and (4) genetic manipulation of Na_V channel function. While the translation of preclinical findings to a viable treatment in humans has remained a challenge, a greater understanding of Na_V channel physiology could lead to the development of a new stream of therapies aimed at alleviating chronic pain.