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

Sang-Min Jeon, J. K. Sung, H. J. Cho

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)354-366
Number of pages13
JournalNeuroscience
Volume190
DOIs
StatePublished - Sep 5 2011
Externally publishedYes

Fingerprint

Rhizotomy
Chemokine CCL2
Tumor Necrosis Factor Receptors
Neuralgia
Sensory Receptor Cells
Spinal Ganglia
Hyperalgesia
Macrophages
Neutralizing Antibodies
Neurons
Spinal Cord
CCR Receptors
Spinal Nerve Roots
Antisense Oligonucleotides
Proteins
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Maintenance

Keywords

  • Macrophage
  • Monocyte chemoattractant protein-1
  • Neuropathic pain
  • Rhizotomy
  • Tumor necrosis factor receptor 1
  • Ventral root

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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title = "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",
abstract = "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.",
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N2 - 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.

AB - 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.

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