Suzuki Munetaka, Inoue Gen, Gemba Takefumi, Watanabe Tomoko, Ito Toshinori, Koshi Takana, Yamauchi Kazuyo, Yamashita Masaomi, Orita Sumihisa, Eguchi Yawara, Ochiai Nobuyasu, Kishida Shunji, Takaso Masashi, Aoki Yasuchika, Takahashi Kazuhisa, Ohtori Seiji
Department of Orthopaedic Surgery, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Eur Spine J. 2009 Jul;18(7):1001-7. doi: 10.1007/s00586-009-0940-x. Epub 2009 Mar 24.
Nuclear factor-kappa B (NF-kappaB) is a gene transcriptional regulator of inflammatory cytokines. We investigated the transduction efficiency of NF-kappaB 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-kappaB 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-kappaB 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-kappaB decoy was transduced into DRGs in vivo. NF-kappaB decoy may be useful as a target for clarifying the mechanism of sciatica caused by lumbar disc herniation.
核因子-κB（NF-κB）是炎症细胞因子的基因转录调节因子。我们研究了NF-κB诱饵对背根神经节（DRG）的转导效率，以及在大鼠腰椎间盘突出症模型中神经损伤、机械性异常性疼痛和热痛觉过敏的减轻情况。本研究使用了40只大鼠。将NF-κB诱饵-异硫氰酸荧光素（FITC）经鞘内注射到5只大鼠的L5水平，测量其向DRG的转导效率。在另外30只大鼠中，对L5水平的DRG施加机械压力，并将从大鼠尾椎间盘获取的髓核移植到DRG上。大鼠被分为三组，每组10只动物：突出+诱饵组、突出+寡核苷酸组和仅突出组。进行行为测试时，评估机械性异常性疼痛和热痛觉过敏。在15只突出大鼠中，切除其左侧L5 DRG，并与5只对照大鼠相比，免疫组织化学评估活化转录因子3（ATF-3）和降钙素基因相关肽（CGRP）的表达。NF-κB诱饵-FITC在DRG神经元中的体内总转导效率为10.8%。突出+诱饵组中CGRP和ATF-3的表达明显低于其他突出组。突出+诱饵组中机械性异常性疼痛和热痛觉过敏得到明显抑制。NF-κB诱饵在体内被转导到DRG中。NF-κB诱饵可能作为阐明腰椎间盘突出症引起坐骨神经痛机制的一个靶点。
