Nav1.9: A unique voltage-gated sodium channel with a role in inflammatory pain.

Abstract

In inflamed tissue, sensitization of pain-sensing neurons results in exaggerated responses to mild or even innocuous stimuli. A substantial part of this increase in neuronal excitability is due to an effect on NaV1.9, an elusive member of the voltage-gated sodium (NaV) channel family that deviates from other subtypes because of its ultra-slow kinetics and hyperpolarized activation voltage. How these exceptional biophysical characteristics affect neurons at baseline and under stimulated conditions is a matter of debate, and this is likely to remain so until the major hurdles impeding its investigation can be eluded. These hurdles entail the difficulty of expression in heterologous expression systems, a lack of pharmacological tools and the general variability encountered in NaV1.9 experimentation. The goal of our research is to understand the reasons behind these complications and to establish a system that allows robust electrophysiological recordings. This work can be a starting point for future studies focusing on NaV1.9 pharmacology or its involvement in inflammatory pain pathways.