Upregulation of Nav1.3 Channel Induced by rrTNF in Cultured Adult Rat DRG Neurons via p38 MAPK and JNK Pathways.
Upregulation of Nav1.3 Channel Induced by rrTNF in Cultured Adult Rat DRG Neurons via p38 MAPK and JNK Pathways.
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DOI：
10.4077/cjp.2011.amm075
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发表时间：
2011-08
期刊：
影响因子：
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通讯作者：
Y. Zang;W. Xin;R. Pang;Yongyong Li;Xian-Guo Liu
中科院分区：
文献类型：
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作者：
Y. Zang;W. Xin;R. Pang;Yongyong Li;Xian-Guo Liu
Activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal protein kinase (JNK) in the dorsal root ganglia (DRG) is critical for the development of neuropathic pain. Tetraodontoxin-sensitive Nav1.3 channel, expressed at a very low level in the adult nervous system, is up-regulated in DRG neurons after peripheral nerve injury or peri-sciatic administration of rat recombinant tumour necrosis factor-alpha (rrTNF-α). To test if activation of p38 MAPK and JNK is required for the re-expression of Nav1.3 channel in cultured adult rat DRG neurons, we administrated rrTNF to cultured adult rat DRG neurons to induce Nav1.3 re-expression, and pre-treated with p38 MAPK inhibitor (SB203580 at 2.65, 26.5 and 265 μM) or JNK inhibitor (SP600125 at 1, 10 and 100 μM) 2 h before rrTNF to observe changes of Nav1.3-immunoreactivity. Compared with the DMSO vehicle pre-treatment group, SB203580 at 2.65 μM partially blocked the re-expression of Nav1.3 (P<0.001), and at 26.5 and 265 μM completely blocked Nav1.3 (P<0.001). Similarly, SP600125 at the concentration of 1 μM blocked the re-expression of Nav1.3 partially (P<0.001), and at 10 and 100 μM blocked Nav1.3 completely (P<0.001). These data show that the activation of both p38 MAPK and JNK in DRG neurons was involved in the re-expression of Nav1.3 channel triggered by TNF-α, which might contribute to neuropathic pain.
