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Neurosci Bull. 2018 Feb;34(1):4-12. doi: 10.1007/s12264-017-0132-3. Epub 2017 Apr 19.

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.

Chang W1,2, Berta T3,4, Kim YH1,5, Lee S6, Lee SY7, Ji RR8,9.

Author information

1
Department of Anesthesiology, Duke University Medical Center, Durham, NC, 27710, USA.
2
Department of Physiology and Biophysics, College of Medicine, Eulji University, Daejeon, Korea.
3
Department of Anesthesiology, Duke University Medical Center, Durham, NC, 27710, USA. temugin.berta@uc.edu.
4
Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, OH, 45267, USA. temugin.berta@uc.edu.
5
Department of Physiology, College of Medicine, Gachon University, Incheon, Korea.
6
Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, OH, 45267, USA.
7
Department of Biochemistry, Duke University Medical Center, Durham, NC, 27710, USA.
8
Department of Anesthesiology, Duke University Medical Center, Durham, NC, 27710, USA. ru-rong.ji@duke.edu.
9
Department of Neurobiology, Duke University Medical Center, Durham, NC, 27710, USA. ru-rong.ji@duke.edu.

Abstract

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.

KEYWORDS:

Dorsal root ganglion; Neuropathic pain; Paclitaxel; Voltage-gated sodium channels

PMID:
28424991
PMCID:
PMC5648619
DOI:
10.1007/s12264-017-0132-3
[Indexed for MEDLINE]
Free PMC Article

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