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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-kappaB) 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-kappaB 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-kappaB 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-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-kappaB is essential for the up-regulation of Nav1.3 by TNF-alpha. Results showed that application of rat recombinant TNF-alpha (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-kappaB

Keywords : Adult,Animals,antagonists & inhibitors,Antioxidants,China,cytology,Ganglia,Spinal,Hyperalgesia,In Vitro Techniques,injuries,Lumbar Vertebrae,Male,metabolism,Motor Neurons,NAV1.3 Voltage-Gated Sodium Channel,Nerve Tissue Proteins,Neuralgia,Neurons,NF-kappa B,Pain,pathology,pharmacology,physiology,prevention & control,Pyrrolidines,Rats,Rats,Sprague-Dawley,Recombinant Proteins,Sensory Receptor Cells,Sodium Channels,Spinal Nerve Roots,Thiocarbamates,Tumor Necrosis Factor-alpha,, Nfkappab,Prevents,Mechanical,Allodynia, sports massage for lower back pain

Date of Publication : 2010 Dec 2

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

Organisation : Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd 2, Guangzhou 510080, PR China

Journal of Publication : Brain Res

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20858468

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Inhibition of NF-kappaB prevents mechanical allodynia induced by spinal ventral root transection and suppresses the re-expression of Nav13 in DRG neurons in vivo and in vitro | Fibromyalgia knots shoulders

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