Modulation of sodium channels as pharmacological tool for pain therapy-highlights and gaps.

Voltage-gated sodium channels are crucially involved in the transduction and transmission of nociceptive signals and pathological pain states. In the past decades, a lot of effort has been spent examining and characterizing biophysical properties of the different sodium channels and their role in signaling pathways. Several gains of function mutations of the sodium channels Nav1.7, Nav1.8, and Nav1.9 are associated with pain disorders. Due to their critical role in nociceptive pathways voltage-gated sodium channels are regarded interesting targets for pharmacological pain treatment. However we still need to fill the gap that exists in the translation of efficacy in preclinical in vitro experiments and in models of pain into the clinic. This review summarizes biological and electrophysiological properties of voltage-gated sodium channels and aims to discuss limitations and promising pharmacological strategies in sodium channel research in the context of pain therapy.