Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav1.3 in DRG neurons in vivo and in vitro.
Activation of nucleus factor-kappaB (NF-κB) in the dorsal root ganglia (DRG) is critical for development of neuropathic pain. The underlying mechanisms, however, are largely unknown. In the present work we tested if the activation of NF-κB is required for re-expression of Nav1.3, which is important for development of neuropathic pain, in uninjured DRG neurons. We found that intrathecal injection of pyrrolidine dithiocarbamate (PDTC), a NF-κB inhibitor, completely blocked the mechanical allodynia induced by L5 ventral root transection (L5-VRT), when applied 30 min before or 8h after operation, but at 7d after L5-VRT the same manipulation had no effect on established allodynia. Pre-treatment with PDTC also prevented the re-expression of Nav1.3 induced by L5-VRT. As our previous work has shown that up-regulation of tumor necrosis factor-alpha (TNF-α) in DRG is responsible for the re-expression of Nav1.3 in uninjured DRG neurons following L5 ventral root injury, we investigated whether activation of NF-κB is essential for the up-regulation of Nav1.3 by TNF-α. Results showed that application of rat recombinant TNF-α (rrTNF) into the cultured normal adult rat DRG neurons increased the immunoreactive (IR) of Nav1.3 localized mainly around the cell membrane and pre-treatment with PDTC blocked the change dose-dependently. The data suggested that injury to ventral root might lead to neuropathic pain and the re-expression of Nav1.3 in primary sensory neurons by activation of NF-κB.
Zang
Ying
Y
Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd 2, Guangzhou 510080, PR China.
He
Xin-Hua
XH
Xin
Wen-Jun
WJ
Pang
Rui-Ping
RP
Wei
Xu-Hong
XH
Zhou
Li-Jun
LJ
Li
Yong-Yong
YY
Liu
Xian-Guo
XG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D006930:Hyperalgesia / Q000378:metabolism / Q000517:prevention & control*; D066298:In Vitro Techniques; D008159:Lumbar Vertebrae; D008297:Male; D009046:Motor Neurons / Q000473:pathology; D062552:NAV1.3 Voltage-Gated Sodium Channel; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism / Q000517:prevention & control; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*; D013126:Spinal Nerve Roots / Q000293:injuries* / Q000473:pathology; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000975:Antioxidants; D062552:NAV1.3 Voltage-Gated Sodium Channel; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D011759:Pyrrolidines; D011994:Recombinant Proteins; C478638:Scn3a protein, rat; D015222:Sodium Channels; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid