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 kappa 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 kappa 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 kappa B inhibitor, completely blocked the mechanical allodynia induced by L5 ventral root transection (L5 VRT), when applied 30 ram before or 8 h after operation, but at 7 d 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-alpha) 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 kappa B is essential for the up regulation of Nav1 3 by TNF alpha Results showed that application of rat recombinant TNF alpha (nTNF) 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-kappa B (C) 2010 Elsevier B V All rights reserved