Na v1.8 expression is not restricted to nociceptors in mouse peripheral nervous system

Abstract

A vast diversity of salient cues is sensed by numerous classes of primary sensory neurons, defined by specific neuropeptides, ion channels, or cytoskeletal proteins. Recent evidence has demonstrated a correlation between the expression of some of these molecular markers and transmission of signals related to distinct sensory modalities (eg, heat, cold, pressure). Voltage-gated sodium channel Na v1.8 has been reported to be preferentially expressed in small-diameter unmyelinated sensory afferents specialized for the detection of noxious stimuli (nociceptors), and Na v1.8-Cre mice have been widely used to investigate gene function in nociceptors. However, the identity of neurons in which Cre-mediated recombination occurs in these animals has not been resolved, and whether expression of Na v1.8 in these neurons is dynamic during development is not known, rendering interpretation of conditional knockout mouse phenotypes problematic. Here, we used genetics, immunohistochemistry, electrophysiology, and calcium imaging to precisely characterize the expression of Na v1.8 in the peripheral nervous system. We demonstrate that 75% of dorsal root ganglion (DRG) neurons express Na v1.8-Cre, including >90% of neurons expressing markers of nociceptors and, unexpectedly, a large population (∼40%) of neurons with myelinated A fibers. Furthermore, analysis of DRG neurons' central and peripheral projections revealed that Na v1.8-Cre is not restricted to nociceptors but is also expressed by at least 2 types of low-threshold mechanoreceptors essential for touch sensation, including those with C and Aβ fibers. Our results indicate that Na v1.8 underlies electrical activity of sensory neurons subserving multiple functional modalities, and call for cautious interpretation of the phenotypes of Na v1.8-Cre-driven conditional knockout mice. © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.