Review

SCN8A (NaV1.6): Gate to Chronic Pain

Wenrui Xie , Judith A. Strong , Jun-Ming Zhang
Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
J Anesth Perioper Med 2018; 5(x): x- xx . Published on Nov 3, 2018 . doi:10.24015/JAPM.2018.0100
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Abstract

Aim of review: Sodium channels are large transmembrane proteins with a voltage-gated pore capable of selectively conducting Na+. They are critical determinants of the electrical excitability of sensory neurons and play a key role in pain sensation. Injury and disease affecting peripheral nerves induce neuropathic changes, and increase cellular excitability due to subtype-specific abnormalities in the expression and trafficking of sodium channels. In this review, we present an overview of current research on sodium channel isoform 1.6 (NaV1.6) and the β4 subunit (NaVβ4) in pathological pain conditions. 
 
Methods: We first provide a brief description of the sodium channel isoforms and their roles in neuronal excitability and pain. We then focus on recent findings from our lab regarding the expression and changes of NaV1.6 and NaVβ4 in sensory neurons under physiological and pathological conditions, and how they contribute to the development and maintenance of pathological pain.
 
Recent findings: Over the last decade, studies on transgenic mice and human mutations have revealed that many sodium channel isoforms such as NaV1.3, NaV1.7, NaV1.8, 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-frequency 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.)  

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