The up-regulation of IL-6 in DRG and spinal dorsal horn contributes to neuropathic pain following L5 ventral root transection.

Abstract

Our previous works have shown that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) plays an important role in neuropathic pain produced by lumber 5 ventral root transection (L5-VRT). In the present work we evaluate the role of interleukin-6 (IL-6), another key inflammatory cytokine, in the L5-VRT model. We found that IL-6 was up-regulated in the ipsilateral L4 and L5 dorsal root ganglian (DRG) neurons and in bilateral lumbar spinal cord following L5-VRT. Double immunofluorescence stainings revealed that in DRGs the increased immunoreactivity (IR) of IL-6 was almost restricted in neuronal cells, while in the spinal dorsal horn IL-6-IR up-regulated in both glial cells (astrocyte and microglia) and neurons. Intrathecal administration of IL-6 neutralizing antibody significantly delayed the induction of mechanical allodynia in bilateral hindpaws after L5-VRT. Furthermore, inhibition of TNF-α synthesis by intraperitoneal thalidomide prevented both mechanical allodynia and the up-regulation of IL-6 in DRGs following L5-VRT. These data suggested that the increased IL-6 in afferent neurons and spinal cord contribute to the development of neuropathic pain following motor fiber injury, and that TNF-α is responsible for the up-regulation of IL-6.

• Authors: Xu-Hong Wei, Xiao-Dong Na, Guang-Jie Liao, Qiu-Ying Chen, Yu Cui, Feng-Ying Chen, Yong-Yong Li, Ying Zang, Xian-Guo Liu
• Journal: Experimental neurology (Exp Neurol) Vol. 241 Pg. 159-68 (Mar 2013) ISSN: 1090-2430 [Electronic] United States
• PMID: 23261764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Activating Transcription Factor 3
• Atf3 protein, rat
• CD11b Antigen
• Interleukin-6
• Lectins
• Nerve Tissue Proteins
• Tumor Necrosis Factor-alpha

Topics

• Activating Transcription Factor 3 (metabolism)
• Analysis of Variance
• Animals
• CD11b Antigen (metabolism)
• Disease Models, Animal
• Functional Laterality
• Hyperalgesia (etiology)
• Interleukin-6 (metabolism)
• Lectins (metabolism)
• Male
• Nerve Tissue Proteins (metabolism)
• Neuralgia (etiology, pathology)
• Pain Threshold (physiology)
• Polyradiculopathy (complications, etiology)
• Rats
• Rats, Sprague-Dawley
• Spinal Nerve Roots (metabolism, pathology)
• Spinal Nerves (injuries)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)
• Up-Regulation (physiology)