Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model

Spine (Phila Pa 1976). 2013 Nov 1;38(23):2003-7. doi: 10.1097/BRS.0b013e3182a84701.

Abstract

Study design: A prospective molecular mechanism of macrophages infiltration in experimental disc herniation.

Objective: To investigate the mechanisms of macrophages infiltration into the dorsal root ganglion (DRG) in a rat model of disc herniation.

Summary of background data: Macrophages infiltrate the DRG after application of nucleus pulposus (NP) on the DRG, and may play an important role in radiculopathy. However, the mechanisms of macrophages infiltration after NP application remain poorly understood.

Methods: After experimental disc herniation in this study, we investigated changes in the expression of ED1 (a marker of macrophages) and vascular cell adhesion molecule-1 (VCAM-1) in DRG using immunofluorescence. We also investigated the expression of ED1 and VCAM-1 in DRG by treatment with tumor necrosis factor-α (TNF-α) inhibitor at the time of surgery.

Results: We found a massive ED1-positive macrophages infiltrated the DRG, and VCAM-1-like immunoreactivity vessels became evident after NP application. Furthermore, both macrophage infiltration and VCAM-1 expression were prevented by treatment with TNF-α inhibitor at the time of surgery.

Conclusion: These findings indicated that macrophages infiltration into the DRG was TNF-α-dependent, and might be partly mediated by VCAM-1 in the early stage of experimental lumbar disc herination. Taken together, this study provides important preliminary data suggesting that TNF-α plays an important role in the macrophage infiltration.

Level of evidence: N/A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemotaxis* / drug effects
  • Disease Models, Animal
  • Ectodysplasins / metabolism
  • Etanercept
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / immunology
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / pathology
  • Immunoglobulin G / pharmacology
  • Intervertebral Disc Displacement / immunology
  • Intervertebral Disc Displacement / metabolism*
  • Intervertebral Disc Displacement / pathology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Tumor Necrosis Factor
  • Signal Transduction
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Ectodysplasins
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Etanercept