Nuclear factor-kappa B decoy suppresses nerve injury and improves mechanical allodynia and thermal hyperalgesia in a rat lumbar disc herniation model

被引:46
作者
Suzuki, Munetaka [1 ]
Inoue, Gen [1 ]
Gemba, Takefumi [2 ]
Watanabe, Tomoko [1 ]
Ito, Toshinori [1 ]
Koshi, Takana [1 ]
Yamauchi, Kazuyo [1 ]
Yamashita, Masaomi [1 ]
Orita, Sumihisa [1 ]
Eguchi, Yawara [1 ]
Ochiai, Nobuyasu [1 ]
Kishida, Shunji [1 ]
Takaso, Masashi [1 ]
Aoki, Yasuchika [1 ]
Takahashi, Kazuhisa [1 ]
Ohtori, Seiji [1 ]
机构
[1] Chiba Univ, Grad Sch Med, Dept Orthopaed Surg, Chuo Ku, Chiba 2608670, Japan
[2] AnGes MG Inc, Dept Pharmaceut, Osaka, Japan
关键词
Nuclear factor-kappa B; Decoy; Nerve injury; Pain; Lumbar disc herniation; NECROSIS-FACTOR-ALPHA; DORSAL-ROOT GANGLION; NITRIC-OXIDE SYNTHASE; GENE-RELATED PEPTIDE; HISTOLOGIC-CHANGES; INFLAMMATORY DISEASES; RHEUMATOID-ARTHRITIS; INDUCED SCIATICA; CYCLOSPORINE-A; MESSENGER-RNA;
D O I
10.1007/s00586-009-0940-x
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Nuclear factor-kappa B (NF-kappa B) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-kappa B decoy to dorsal root ganglion (DRG), as well as the decrease in nerve injury, mechanical allodynia, and thermal hyperalgesia in a rat lumbar disc herniation model. Forty rats were used in this study. NF-kappa B decoy-fluorescein isothiocyanate (FITC) was injected intrathecally at the L5 level in five rats, and its transduction efficiency into DRG measured. In another 30 rats, mechanical pressure was placed on the DRG at the L5 level and nucleus pulposus harvested from the rat coccygeal disc was transplanted on the DRG. Rats were classified into three groups of ten animals each: a herniation + decoy group, a herniation + oligo group, and a herniation only group. For behavioral testing, mechanical allodynia and thermal hyperalgesia were evaluated. In 15 of the herniation rats, their left L5 DRGs were resected, and the expression of activating transcription factor 3 (ATF-3) and calcitonin gene-related peptide (CGRP) was evaluated immunohistochemically compared to five controls. The total transduction efficiency of NF-kappa B decoy-FITC in DRG neurons was 10.8% in vivo. The expression of CGRP and ATF-3 was significantly lower in the herniation + decoy group than in the other herniation groups. Mechanical allodynia and thermal hyperalgesia were significantly suppressed in the herniation + decoy group. NF-kappa B decoy was transduced into DRGs in vivo. NF-kappa B decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.
引用
收藏
页码:1001 / 1007
页数:7
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