Therapy of neuropathic pain by using a gene-based approach of NF-κB decoy

使用基于基因的 NF-κB 诱饵方法治疗神经性疼痛

• 批准号: 12557130
• 负责人: MASHIMO Takashi
• 金额: $ 8.19万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12557130/
• 关键词: NF-κB; decoy; heuropathic pain; cytokine; HVJ-liposome; 遺伝子導入; ベクター; デコイ; HVJ-liposome; 疼痛過敏

Pro-inflammatory cytokines have been shown to be involved in the genesis, persistence, and severity of neuropathic pain following nerve injury. The transcription factor, nuclear factor-kappa B (NF-κB), palys a pivotal role in regulating pro-inflammatory cytokine gene expression. To elucidate the role of NF-κB in the pathogenesis of neuropathic pain, using a gene-based approach of NF-κB decoy, we tested whether the activated NF-κB affected pain behavior via the expression of inflammatory mediators. Single endoneurial injections' of, NF-κB decoy, at the site of nerve lesion, significantly alleviated thermal hyperalgesia for up to 2 weeks and suppressed the expression of mRNA of the inflammatory cytokines, iNOS, and adhesion molecules at the site of nerve injury. This finding suggests that a perineural inflammatory cascade, that involves NF-κB, is involved in the pathogenesis of neuropathic pain

促炎细胞因子已被证明参与神经损伤后神经病理性疼痛的发生、持续和严重程度。核因子-κ B（NF-κB）是一种重要的转录因子，在调节促炎细胞因子基因表达中起着重要作用。为了阐明NF-κB在神经病理性疼痛发病机制中的作用，我们采用基于基因的NF-κB诱饵方法，检测了活化的NF-κB是否通过炎症介质的表达影响疼痛行为。在神经损伤部位单次神经内注射NF-κB诱饵，可显著减轻热痛觉过敏长达2周，并抑制神经损伤部位炎性细胞因子、iNOS和粘附分子的mRNA表达。这一发现表明，一个涉及NF-κB的神经周围炎症级联反应参与了神经病理性疼痛的发病机制

项目成果

Hashimoto N, Yamanaka H, Fukuoka T, Dai Y, Obata K, Mashimo T, Noguchi K: "Expression of HGF and cMet in the peripheral nervous system of adults rats following sciatic nerve injury."NeuroReport. 12. 1403-1407 (2001)

Hashimoto N、Yamanaka H、Fukuoka T、Dai Y、Obata K、Mashimo T、Noguchi K：“坐骨神经损伤后成年大鼠周围神经系统中 HGF 和 cMet 的表达。”NeuroReport。

Sakaue G, Shimaoka M, Fukuoka T, et al.: "NF-kB decoy supresses cytokine expression and thermal hyperalgesia in rat neuropathic pain model"NeuroReport. 12. 2079-2084 (2001)

Sakaue G、Shimaoka M、Fukuoka T 等人：“NF-kB 诱饵抑制大鼠神经性疼痛模型中的细胞因子表达和热痛觉过敏”NeuroReport。

Hashimoto N, Yamanaka H, Fukuoka T, Obata K, Mashimo T, Noguchi K.: "Expression of hepatocyte growth factor in primary sensory neurons of adult rats."Mol Brain Res. 97. 83-88 (2001)

Hashimoto N、Yamanaka H、Fukuoka T、Obata K、Mashimo T、Noguchi K.：“成年大鼠初级感觉神经元中肝细胞生长因子的表达。”Mol Brain Res。

Sakaue G, Shimaoka M, Fukuoka T, Hiroi T, Inoue T, Hashimoto N, Sakaguchi T, Sawa Y, Moricita R, Kiyono H, Noguchi K, Mashimo T.: "NF-κB decoy supresses cytokine expression and thermal hyperalgesia in a rat neuropatic pain model"NeuroReport. 12. 2079-2084

Sakaue G、Shimaoka M、Fukuoka T、Hiroi T、Inoue T、Hashimoto N、Sakaguchi T、Sawa Y、Moricita R、Kiyono H、Noguchi K、Mashimo T.：“NF-κB 诱饵抑制细胞因子表达和热痛觉过敏大鼠神经病理性疼痛模型《NeuroReport.12.2079-2084》

Sakaue G, Shimaoka M, Fukuoka T, Hiroi T, Inoue T, Hashimoto N, Sakaguchi T, Sawa Y, Morishita R, Kiyono H, Noguchi K, Mashimo T: "NF-κB decoy supresses cytokine expression and thermal hyperalgesia in a rat neuropathic pain model."NeuroReport. 12. 2079-20

Sakaue G、Shimaoka M、Fukuoka T、Hiroi T、Inoue T、Hashimoto N、Sakaguchi T、Sawa Y、Morishita R、Kiyono H、Noguchi K、Mashimo T：“NF-κB 诱饵抑制大鼠细胞因子表达和热痛觉过敏神经病理性疼痛模型。”NeuroReport. 12. 2079-20