UC Davis

Voltage-gated sodium (Na_V) channels are critical molecular determinants of action potential generation and propagation in excitable cells. Normal Na_V channel function disruption can affect physiological neuronal signaling and lead to increased sensitivity to pain, congenital indifference to pain, uncoordinated movement, seizures, or paralysis. Human genetic studies have identified human Na_V1.7 (hNa_V1.7), hNa_V1.8, and hNa_V1.9 channel subtypes as crucial players in pain signaling. The premise that subtype selective Na_V inhibitors can reduce pain has been reinforced through intensive target validation and therapeutic development efforts. However, an ideal therapeutic has yet to emerge. This review is focused on recent progress, current challenges, and future opportunities to develop Na_V channel targeting small molecules and peptides as non-addictive therapeutics to treat pain.