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Tumor necrosis factor receptor 1 induces interleukin‐6 upregulation through NF‐kappaB in a rat neuropathic pain model
Author(s) -
Lee KyungMin,
Jeon SangMin,
Cho HeeJung
Publication year - 2009
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1016/j.ejpain.2008.09.009
Subject(s) - downregulation and upregulation , neuropathic pain , spinal cord , p38 mitogen activated protein kinases , tumor necrosis factor alpha , mapk/erk pathway , medicine , sciatic nerve , endocrinology , cancer research , phosphorylation , anesthesia , chemistry , microbiology and biotechnology , biology , biochemistry , psychiatry , gene
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.