Expression and Role of Voltage-Gated Sodium Channels in Human Dorsal Root Ganglion Neurons with Special Focus on Nav1.7, Species Differences, and Regulation by Paclitaxel.

Published

Journal Article

Voltage-gated sodium channels (Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion (hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Nav1.7 (~50% of total Nav expression) and lower expression of Nav1.8 (~12%), whereas the mouse DRG has higher expression of Nav1.8 (~45%) and lower expression of Nav1.7 (~18%). To mimic Nav regulation in chronic pain, we treated hDRG neurons in primary cultures with paclitaxel (0.1-1 μmol/L) for 24 h. Paclitaxel increased the Nav1.7 but not Nav1.8 expression and also increased the transient Na+ currents and action potential firing frequency in small-diameter (<50 μm) hDRG neurons. Thus, the hDRG provides a translational model in which to study "human pain in a dish" and test new pain therapeutics.

Full Text

Duke Authors

Cited Authors

  • Chang, W; Berta, T; Kim, YH; Lee, S; Lee, S-Y; Ji, R-R

Published Date

  • February 2018

Published In

Volume / Issue

  • 34 / 1

Start / End Page

  • 4 - 12

PubMed ID

  • 28424991

Pubmed Central ID

  • 28424991

Electronic International Standard Serial Number (EISSN)

  • 1995-8218

Digital Object Identifier (DOI)

  • 10.1007/s12264-017-0132-3

Language

  • eng

Conference Location

  • Singapore