Injection of nuclear factor-kappa B decoy into the sciatic nerve suppresses mechanical allodynia and thermal hyperalgesia in a rat inflammatory pain model
Injection of nuclear factor-kappa B decoy into the sciatic nerve suppresses mechanical allodynia and thermal hyperalgesia in a rat inflammatory pain model
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DOI：
10.1097/01.brs.0000248424.46652.67
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发表时间：
2006-12-01
期刊：
影响因子：
3
通讯作者：
Takahashi, Kazuhisa
中科院分区：
文献类型：
--
作者：
Inoue, Gen;Ochiai, Nobuyasu;Takahashi, Kazuhisa
研究设计。利用核因子-kappa B诱饵建立大鼠炎症性疼痛模型的体内外研究。目的：研究核因子-kappa B诱饵在体内和体外对背根神经节的转导效率，并评价核因子-kappa B诱骗对炎性疼痛的抑制作用。据报道，转录因子核因子-kappaB在调节促炎细胞因子基因表达中起着关键作用。我们假设用核因子-kappa B诱饵抑制核因子-kappaB基因的表达可能会抑制炎性疼痛。在组织块培养中诱导核因子-kappa B诱骗荧光素异硫氰酸酯(FITC)，将其注入坐骨神经内，并测定其对背根节的转导效率。为进行行为学测试，12只大鼠足底注射完全弗氏佐剂，随机分为3组：诱饵组，单次神经内注射10亩L核因子-kappa B诱饵(n=4)，生理盐水组，单次神经内注射10亩L生理盐水(n=4)，以及单纯组(n=4)。使用von Frey灯丝和带有热源的Hargreaves装置进行行为测试。核因子-kappa B诱骗FITC的体外总转导效率为53.6%，体内总转导效率为20.5%。所有FITC阳性神经元的细胞大小分布类型没有统计学差异。在行为学测试中，在机械性痛觉过敏实验中，假手术组与生理盐水组在术后2~14d，在热痛觉过敏实验中，在术后2~3d，假手术组与生理盐水组的戒断潜伏期或阈值有显著差异。在体内和体外，核因子-kappa B诱饵被运送和转导到背根神经节。此外，核因子-kappa B诱饵可减少炎性痛模型大鼠的机械性痛觉过敏和热痛觉过敏，提示核因子-kappa B诱骗抑制核因子-kappaB可能是介导炎症或减轻炎性疼痛的关键机制。
Study Design. In vitro and in vivo study of a rat inflammatory pain model using nuclear factor-kappa B decoy.Objectives. To investigate transduction efficiency of nuclear factor-kappa B decoy into dorsal root ganglion, both in vivo and in vitro, and to assess the suppression of inflammatory pain by nuclear factor-kappa B decoy.Summary of Background Data. Transcription factor nuclear factor-kappa B is reported to play a crucial role in regulating pro-inflammatory cytokine gene expression. We hypothesized that inhibiting nuclear factor-kappa B gene expression with nuclear factor-kappa B decoy may suppress inflammatory pain.Methods. Nuclear factor-kappa B decoy-fluorescein isothiocyanate ( FITC) was induced in explant culture, endoneurally injected into the sciatic nerve, and its transduction efficiency into dorsal root ganglion measured. For behavioral testing, 12 rats received plantar injections of complete Freund's adjuvant and were divided into 3 groups: decoy group, single endoneural injection of 10 mu L of nuclear factor-kappa B decoy ( n = 4); saline group, single endoneural injection of 10 mu L of saline ( n = 4); and naive group, untreated ( n = 4). Behavioral testing was performed using von Frey filaments and a Hargreaves device with a heat source.Results. Total transduction efficiency of nuclear factor-kappa B decoy-FITC was 53.6% in vitro and 20.5% in vivo. No statistical differences were observed with respect to types of cell size distributions of all FITC-positive neurons. In behavioral testing, withdrawal latencies or thresholds significantly differed between the decoy group and the saline group from 2 to 14 days after surgery in the mechanical allodynia experiments, and from 2 to 3 days after surgery in the thermal hyperalgesia experiments.Conclusions. Nuclear factor-kappa B decoy was conveyed and transduced into dorsal root ganglion both in vivo and in vitro. Additionally, nuclear factor-kappa B decoy reduced mechanical allodynia and thermal hyperalgesia in the rat inflammatory pain model, suggesting that inhibition of nuclear factor-kappa B with nuclear factor-kappa B decoy may represent a key mechanism for mediating inflammation or reducing inflammatory pain.