Tumor necrosis factor receptor 1 induces interleukin-6 upregulation through NF-kappaB in a rat neuropathic pain model |
| |
Authors: | Kyung-Min Lee Sang-Min Jeon Hee-Jung Cho |
| |
Affiliation: | aDepartment of Anatomy, School of Medicine, Kyungpook National University, 2-101, Dongin-Dong, Daegu 700-422, South Korea |
| |
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. |
| |
Keywords: | Peripheral nerve injury Neuropathic pain mechanism Interleukin-6 p38 MAPK NF-κ B |
本文献已被 ScienceDirect 等数据库收录! |
|