1Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
2Department of Physiology and Biophysics, College of Medicine, Eulji University, Daejeon, Korea
3Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA
4Department of Physiology, College of Medicine, Gachon University, Incheon, Korea
5Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
6Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA

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

[SpringerLink]