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

Exp Neurol. 2013 Mar;241:159-68. doi: 10.1016/j.expneurol.2012.12.007. Epub 2012 Dec 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Neuralgia / pathology*
  • Pain Threshold / physiology
  • Polyradiculopathy / complications*
  • Polyradiculopathy / etiology
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Nerve Roots / metabolism*
  • Spinal Nerve Roots / pathology
  • Spinal Nerves / injuries
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / physiology*

Substances

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