SCN8A (NaV1.6): Gate to Chronic Pain

and NaV1.9 are involved in different aspects of physiological or pathological pain. Although NaV1.6 in conjunction with the modulatory NaVβ4 subunit has the ability to trigger and maintain high-frequency repetitive firing via mediating persistent and resurgent currents, only very recently has its role in pain disorders been recognized. Summary: The persistent and resurgent currents in sensory neurons are generated predominantly by NaV1.6 in association with NaVβ4. Since spontaneous activity, especially high-fre-quency repetitive and burst firing in damaged peripheral sensory nerve or neurons, is crucial for the development of neuropathic pain, NaV1.6 and/or NaVβ4 may be new therapeutic targets for managing pathological pain conditions. (Funded by the National Institutes of Health.) ABSTRACT