title: Upregulation of Nav1.3 Channel Induced by rrTNF in Cultured Adult Rat DRG Neurons via p38 MAPK and JNK Pathways.
abstract: 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.
authors: Pain Research Center and Department of Physiology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou 510080, Guangdong, People's Republic of China.
authors: Ying
authors: Y
authors: Zang
authors: Wen-Jun
authors: WJ
authors: Xin
authors: Rui-Ping
authors: RP
authors: Pang
authors: Yong-Yong
authors: YY
authors: Li
authors: Xian-Guo
authors: XG
authors: Liu
mesh_terms: D000818:Animals; D020935:MAP Kinase Signaling System; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases