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

被引:105
作者
Chang, Wonseok [1 ,2 ]
Berta, Temugin [1 ,3 ]
Kim, Yong Ho [1 ,4 ]
Lee, Sanghoon [3 ]
Lee, Seok-Yong [5 ]
Ji, Ru-Rong [1 ,6 ]
机构
[1] Duke Univ, Dept Anesthesiol, Med Ctr, Durham, NC 27710 USA
[2] Eulji Univ, Dept Physiol & Biophys, Coll Med, Daejeon, South Korea
[3] Univ Cincinnati, Dept Anesthesiol, Pain Res Ctr, Med Ctr, Cincinnati, OH 45267 USA
[4] Gachon Univ, Dept Physiol, Coll Med, Incheon, South Korea
[5] Duke Univ, Dept Biochem, Med Ctr, Durham, NC 27710 USA
[6] Duke Univ, Dept Neurobiol, Med Ctr, Durham, NC 27710 USA
关键词
Dorsal root ganglion; Neuropathic pain; Paclitaxel; Voltage-gated sodium channels; PAIN; ACTIVATION; NA(V)1.8; SENSITIZATION; CONTRIBUTES; MUTATIONS; MODELS; TRPV1;
D O I
10.1007/s12264-017-0132-3
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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 mu mol/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 mu m) hDRG neurons. Thus, the hDRG provides a translational model in which to study "human pain in a dish" and test new pain therapeutics.
引用
收藏
页码:4 / 12
页数:9
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