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.

By London Spine

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.

Brain Res. 2010 Dec 2;1363:151-8

Authors: Zang Y, He XH, Xin WJ, Pang RP, Wei XH, Zhou LJ, Li YY, Liu XG

Activation of nucleus factor-kappaB (NF-?B) 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-?B 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-?B 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-?) 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-?B is essential for the up-regulation of Nav1.3 by TNF-?. Results showed that application of rat recombinant TNF-? (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-?B.

PMID: 20858468 [PubMed – indexed for MEDLINE]