Use-dependent inhibitors of voltage-gated sodium channels (VGSC) are important therapeutic tools for chronic pain management, but are limited by possible severe side effects. Recent studies have provided much new information on the function of several voltage-gated sodium channels that are predominantly expressed in peripheral sensory neurons, and on their possible link to pathological pain states arising from injuries to the sensory nerve. The use of antisense oligonucleotides to target specific channel subtypes shows that the functional localization of the channel subtype NaV1.8 after nerve injury is essential for persistent pain states. The putative roles of NaV1.3 and NaV1.9 in neuropathic pain are also discussed. These studies may form a basis for developing inhibitors to target specific channel subtype(s) for use in chronic pain treatment.
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