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Stromal Cell-Derived Factor 1 Increases Tetrodotoxin-Resistant Sodium Currents Nav1.8 and Nav1.9 in Rat Dorsal Root Ganglion Neurons via Different Mechanisms

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Abstract

Stromal cell-derived factor 1 (SDF-1)/chemokine CXC motif ligand 12 (CXCL12), a chemokine that is upregulated in dorsal root ganglion (DRG) during chronic pain models, has recently been found to play a central role in pain hypersensitivity. The purpose of present study is to investigate the functional impact of SDF-1 and its receptor, chemokine CXC motif receptor 4 (CXCR4), on two TTXR sodium channels in rat DRG using electrophysiological techniques. Preincubation with SDF-1 caused a concentration-dependent increase of Nav1.8 and Nav1.9 currents amplitudes in acutely isolated small diameter DRG neurons in short-term culture. As to Nav1.9, changes in current density and kinetic properties of Nav1.9 current evoked by SDF-1(50 ng/ml) was eliminated by CXCR4 antagonist AMD3100 and phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. The increase in Nav1.9 current was also blocked by pertussis toxin (PTX) but not cholera toxin (CTX), showing involvement of Gi/o but not Gs subunits. As to Nav1.8, inhibitors (AMD3100, PTX, CTX, LY294002) used in present study didn’t inhibit the increased amplitude of Nav1.8 current and shifted activation curve of Nav1.8 in a hyperpolarizing direction in the presence of SDF-1 (50 ng/ml). In conclusion, our data demonstrated that SDF-1 may excite primary nociceptive sensory neurons by acting on the biophysical properties of Nav1.8 and Nav1.9 currents but via different mechanisms.

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Acknowledgments

The project was financially supported by the National Natural Science Foundation (Grant 30901398). The authors thank Yue-Juan Li and Fang Li for all the helpful suggestions during the revision of original manuscript.

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Authors and Affiliations

  1. Anesthesia and Operation Center, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China

    Fang Qiu, Qiang Fu, Yan-Hong Liu & Wei-Dong Mi

  2. Institute of Geriatric Cardiology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, China

    Yang Li, Yong-Yan Fan & Chao Zhu

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  1. Fang Qiu
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Qiu, F., Li, Y., Fu, Q. et al. Stromal Cell-Derived Factor 1 Increases Tetrodotoxin-Resistant Sodium Currents Nav1.8 and Nav1.9 in Rat Dorsal Root Ganglion Neurons via Different Mechanisms. Neurochem Res 41, 1587–1603 (2016). https://doi.org/10.1007/s11064-016-1873-5

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