Expression of monocyte chemoattractant protein-1 and its induction by tumor necrosis factor receptor 1 in sensory neurons in the ventral rhizotomy model of neuropathic pain

Neuroscience. 2011 Sep 8;190:354-66. doi: 10.1016/j.neuroscience.2011.06.036. Epub 2011 Jun 25.


The expression and role of monocyte chemoattractant protein-1 (MCP-1) in the rat dorsal root ganglion (DRG) and spinal cord was evaluated in the lumbar 5 ventral rhizotomy (L5 VR) model of neuropathic pain. MCP-1 protein expression in the L4/L5 DRG neurons following L5 VR peaked after 3 days, and then declined. Immunohistochemistry showed that no MCP-1 immunoreactivity was observed in the spinal cord after L5 VR, while enzyme-linked immunosorbent assay (ELISA) revealed a small but significant increase in MCP-1 protein content. L5 VR resulted in robust and prolonged mechanical allodynia and thermal hyperalgesia. Administration of anti-MCP-1 neutralizing antibody before and at early time points after L5 VR resulted in a significant attenuation of mechanical allodynia and thermal hyperalgesia, while post-treatment had a weaker effect on established neuropathic pain. Extensive colocalization of tumor necrosis factor receptor 1 (TNFR1) and MCP-1 was observed in the L5 DRG following L5 VR, and treatment with TNFR1 antisense oligonucleotide reduced L5 VR-induced MCP-1 expression in L5 DRG neurons and neuropathic pain behaviors. MCP-1/chemokine (C-C motif) receptor 2 signaling has been proposed as a major regulator of macrophage trafficking. In contrast to the effect on pain behaviors, however, intrathecal administration of anti-MCP-1 neutralizing antibody had no effect on the L5 VR-induced increase in ED-1-immunoreactive macrophages in the L5 DRG and the distal stump of the transected L5 ventral root. These data indicate that increased MCP-1 in DRG neurons might participate in the initiation, rather than the maintenance, of neuropathic pain induced by L5 VR. Furthermore, increased MCP-1 in the DRG is induced by TNF-α/TNFR1 and has no effect on the infiltration of macrophages into the DRG following L5 VR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / metabolism*
  • Disease Models, Animal
  • Ganglia, Spinal / metabolism*
  • Ganglia, Spinal / physiopathology
  • Hyperalgesia / metabolism
  • Hyperalgesia / physiopathology
  • Male
  • Neuralgia / metabolism*
  • Neuralgia / physiopathology
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Tumor Necrosis Factor, Type I / metabolism*
  • Rhizotomy
  • Sensory Receptor Cells / metabolism*
  • Spinal Cord / metabolism*
  • Spinal Cord / physiopathology


  • Chemokine CCL2
  • Receptors, Tumor Necrosis Factor, Type I