Voltage-gated sodium channels (Na_V) are essential for the generation of action potentials and for cell excitability¹. Na_V channels are activated in response to depolarization and selectively allow the flow of Na⁺ ions. To date, nine Na_V α subunits have been cloned and named Na_V1.1-Na_V1.9^4-5. The Na_V channels are classified into two groups according to their sensitivity to tetrodotoxin (TTX): TTX-sensitive (Na_V1.1, Na_V1.2, Na_V1.3, Na_V1.4, Na_V1.6 and Na_V1.7) and TTX-resistant (Na_V1.5, Na_V1.8 and Na_V1.9)^2-3.

Mammalian sodium channels are heterotrimers composed of a central, pore-forming α subunit and two auxiliary β subunits. The expression of the α subunit isoform is developmentally regulated and tissue specific. Na⁺ channels in the adult central nervous system and heart contain β₁ through β₄ subunits, whereas Na⁺ channels in adult skeletal muscle have only the β₁ subunit^6,8.

Na_V1.7 is predominantly expressed in dorsal root ganglions (DRG) of the peripheral nervous system. Dominant gain of function mutations in the Na_V1.7 gene are associated with erythermalgia (a rare autosomal disease characterized by sporadic burning pain accompanied by redness and heat in the extremities).^9-11 Loss of function mutations in Na_V1.7 channels leads to complete ablation of pain perception in humans.¹¹ These recent findings highlight the role of this Na_V isoform and the subset of DRG neurons that express this channel in physiological pain sensation.