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

作者：Zang, Ying^*; Xin, Wen-Jun; Pang, Rui-Ping; Li, Yong-Yong; Liu, Xian-Guo

来源：Chinese Journal of Physiology, 2011, 54(4): 241-246.

DOI：10.4077/CJP.2011.AMM075

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

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 upregulated in DRG neurons after peripheral nerve injury or peri-sciatic administration of rat recombinant tumour necrosis factor-alpha (rrTNF-alpha). 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 mu M) or JNK inhibitor (SP600125 at 1, 10 and 100 mu M) 2 h before rrTNF to observe changes of Nav1.3-immunoreactivity. Compared with the DMSO vehicle pre-treatment group, SB203580 at 2.65 mu M partially blocked the re-expression of Nav1.3 (P < 0.001), and at 26.5 and 265 mu M completely blocked Nav1.3 (P < 0.001). Similarly, SP600125 at the concentration of 1 mu M blocked the re-expression of Nav1.3 partially (P < 0.001), and at 10 and 100 mu M 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-alpha, which might contribute to neuropathic pain.

• 出版日期2011-8-31
• 单位中山大学