Tetrodotoxin, a Candidate Drug for Nav1.1-Induced Mechanical Pain?

Tetrodotoxin (TTX), the mode of action of which has been known since the 1960s, is widely used in pharmacology as a specific inhibitor of voltage-gated sodium channels (Nav channels). This toxin has contributed to the characterization of the allosteric model of the Nav channel, and to discriminating TTX-sensitive and TTX-resistant subtypes. In addition to its role as a pharmacological tool, TTX is now considered a therapeutic molecule, and its development should lead to its use in certain pathologies involving Nav channels, particularly in the field of pain. Specifically, the blockade of Nav channels expressed in nociceptive fibres is one strategy for alleviating pain and its deleterious consequences on health. Recent work has identified, in addition to the Nav1.7, 1.8 and 1.9 channels, the Nav1.1 subtype on dorsal root ganglion (DRG) neurons as a crucial player in mechanical and non-thermal pain. The sensitivity of Nav1.1 to TTX could be exploited at the therapeutic level, especially in chronic pain conditions.