Tumor necrosis factor receptor 1 induces interleukin-6 upregulation through NF-kappaB in a rat neuropathic pain model

Kyung Min Lee, Sang-Min Jeon, Hee Jung Cho

Research output: Contribution to journalArticle

Abstract

Peripheral nerve injury resulting in neuropathic pain induces the upregulation of interleukin (IL)-6 and tumor necrosis factor-α, which binds to tumor necrosis factor receptor 1 (TNFR1) and induces NF-κB and p38 MAPK activation in the spinal cord and dorsal root ganglia (DRG). We here investigated whether TNFR1 regulates IL-6 expression through NF-κB or p38 MAPK activations in the spinal cord and DRG in rats with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal treatment with a TNFR1 antisense oligonucleotide (ASO) significantly inhibited CCI-elevated IKKs phosphorylation, IkB-α degradation, the nuclear translocation, phosphorylation, and DNA-binding activity of NF-κB, p38 MAPK activation, and IL-6 mRNA and protein expression in the spinal cord and DRG. Interestingly, CCI remarkably elevated IKKα and p65 phosphorylations in the spinal cord rather than in the DRG. In addition, NF-κB decoy, but not p38 MAPK inhibitor, SB203580 reduced CCI-elevated IL-6 expression in the spinal cord and DRG. Therefore, these data suggest that TNFR1 induces IL-6 upregulation and neuropathic pain through NF-κB, but not p38 MAPK activation in the spinal cord and DRG and that the NF-κB/IL-6 pathways in the DRG may be less dependent on TNFR1 than the spinal cord pathway.

Original languageEnglish (US)
Pages (from-to)794-806
Number of pages13
JournalEuropean Journal of Pain
Volume13
Issue number8
DOIs
StatePublished - Sep 1 2009
Externally publishedYes

Fingerprint

NF-kappa B
Tumor Necrosis Factor Receptors
Spinal Ganglia
Neuralgia
Interleukin-6
Spinal Cord
Spinal Nerve Roots
Up-Regulation
p38 Mitogen-Activated Protein Kinases
Constriction
Phosphorylation
Wounds and Injuries
Peripheral Nerve Injuries
Antisense Oligonucleotides
Sciatic Nerve
Tumor Necrosis Factor-alpha
Messenger RNA
DNA
Proteins

Keywords

  • Interleukin-6
  • Neuropathic pain mechanism
  • NF-κB
  • p38 MAPK
  • Peripheral nerve injury

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Tumor necrosis factor receptor 1 induces interleukin-6 upregulation through NF-kappaB in a rat neuropathic pain model. / Lee, Kyung Min; Jeon, Sang-Min; Cho, Hee Jung.

In: European Journal of Pain, Vol. 13, No. 8, 01.09.2009, p. 794-806.

Research output: Contribution to journalArticle

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