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Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn

Joel A Black123*, Noémie Frézel12, Sulayman D Dib-Hajj12 and Stephen G Waxman12

Author Affiliations

1 Department of Neurology and Paralyzed Veterans of America Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, CT, 06510, USA

2 Rehabilitation Research Center, VA Connecticut Healthcare System, West Haven, CT, 06516, USA

3 Neuroscience Research Center (127A) VA Connecticut Healthcare System, 950 Campbell Avenue, West Haven, CT, 06516, USA

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Molecular Pain 2012, 8:82  doi:10.1186/1744-8069-8-82

Published: 7 November 2012

Abstract

Background

Sodium channel Nav1.7 has emerged as a target of considerable interest in pain research, since loss-of-function mutations in SCN9A, the gene that encodes Nav1.7, are associated with a syndrome of congenital insensitivity to pain, gain-of-function mutations are linked to the debiliting chronic pain conditions erythromelalgia and paroxysmal extreme pain disorder, and upregulated expression of Nav1.7 accompanies pain in diabetes and inflammation. Since Nav1.7 has been implicated as playing a critical role in pain pathways, we examined by immunocytochemical methods the expression and distribution of Nav1.7 in rat dorsal root ganglia neurons, from peripheral terminals in the skin to central terminals in the spinal cord dorsal horn.

Results

Nav1.7 is robustly expressed within the somata of peptidergic and non-peptidergic DRG neurons, and along the peripherally- and centrally-directed C-fibers of these cells. Nav1.7 is also expressed at nodes of Ranvier in a subpopulation of Aδ-fibers within sciatic nerve and dorsal root. The peripheral terminals of DRG neurons within skin, intraepidermal nerve fibers (IENF), exhibit robust Nav1.7 immunolabeling. The central projections of DRG neurons in the superficial lamina of spinal cord dorsal horn also display Nav1.7 immunoreactivity which extends to presynaptic terminals.

Conclusions

The expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to preterminal central branches and terminals in the dorsal horn. These data support a major contribution for Nav1.7 in pain pathways, including action potential electrogenesis, conduction along axonal trunks and depolarization/invasion of presynaptic axons. The findings presented here may be important for pharmaceutical development, where target engagement in the right compartment is essential.

Keywords:
Dorsal root ganglia; Dorsal horn; Intraepidermal nerve fiber; Pain pathway; Sodium channel; Spinal cord