Upregulation of Nav1.3 Channel Induced by rrTNF in Cultured Adult Rat DRG Neurons via p38 MAPK and JNK Pathways

Ying Zang ； Wen-Jun Xin ； Rui-Ping Pang ； Yong-Yong Li ； Xian-Guo Liu

《The Chinese Journal of Physiology》 54卷4期 (2011/08) Pp. 241-246

https://doi.org/10.4077/CJP.2011.AMM075

並列摘要

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.

並列關鍵字

tumour necrosis factor-α ； p38 mitogen-activated protein kinase ； c-Jun N-terminal protein kinase ； sodium channel ； neuropathic pain

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