Painful Research: Identification of a Small-Molecule Inhibitor that Selectively Targets Na_v1.8 Sodium Channels

Inhibiting Na_v1.8-dependent nociception. The small molecule A-803467 potently inhibits Na_v1.8 tetrodotoxin-resistant (TTX-R) channels in nociceptive neurons. A-803467 also inhibits action potentials in depolarized neurons or spontaneously active neurons following peripheral inflammation. A-803467 is relatively ineffective at inhibiting Na_v1.7 channels, which are now known to participate in nociception. It is not known, however, whether A-803467 can inhibit Na_v1.9, another TTX-R sodium channel that is expressed in large amounts in nociceptive neurons and can contribute to inflammatory pain. Orange star indicates pain stimulus.