Elucidation of mechanism for induction of pain with knockout mice

阐明基因敲除小鼠诱导疼痛的机制

基本信息

  • 批准号:
    11470044
  • 负责人:
  • 金额:
    $ 2.69万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2000
  • 项目状态:
    已结题

项目摘要

The sensation of pain provides useful warning about occurrence of injury. However, under pathological conditions such as prolonged inflammation, post-operation, and nerve injury, nociceptors in the periphery become activeted and produce spontaneous pain, hyperalgesia and tactile pain (allodynia). We previously demonstrated that 1) intrathecal administration of prostaglandin (PG) E2 and PGF2α induced allodynia, 2) capsaicin-sensitive and-insensitive pathways were involved in induction of allodynia, 3) PGs may produce allodynia by initiating a biochamical cascade of glutamate release from synaptic terminal→activation of NMDA receptor→NO production. 4) PGD2 blocked the PGE2-induced allodynia. In order to clarify the involvement of a given component in induction of allodynia by use of knockout mice, we established partial sciatic nerve ligation method in the knockout mouse and obtained following results.Cyclooxygenases (COXs) are rate-limiting enzymes for PG production. While COX-1 is a constitutive form, COX-2 is an inducible form and considered to be accounted for PG production in inflammation. 1) Although allodynia was induced 1 week after treatment, allodynia was observed in COX-2^<-/-> mice, suggesting that COX-2 was not involved in the induction of allodynia. 2) The COX-1 selective inhibitor, but not the COX-2 selective inhibitor, alleviated pain responses induced by sciatic nerve injury. 3) While allodynia was observed in iNOS^<-/-> mice, pain responses disappeared in NMDA^<-/-> mice. These results demonstrate that excitatory transmission by glutamate activated by PGE2 plays pivotal roles in induction and maintenance of pain following sciatic nerve injury. In order to elucidate the induction and maintenance of allodynia, we will extend this study of sciatic nerve injury model and compare it with that of i.t. PG allodynia model.
疼痛的感觉提供了关于损伤发生的有用警告。然而,在病理条件下,例如长期炎症、手术后和神经损伤,外周中的伤害感受器被激活并产生自发性疼痛、痛觉过敏和触觉疼痛(异常性疼痛)。我们以前的研究表明:1)鞘内注射前列腺素(PG)E2和PGF_(2 α)可诱导痛觉超敏; 2)辣椒素敏感和不敏感通路参与痛觉超敏的诱导; 3)PG可能通过启动突触末梢谷氨酸释放→ NMDA受体激活→NO产生的生物化学级联反应而产生痛觉超敏。4)PGD 2可阻断PGE 2诱导的痛觉超敏反应。为了阐明特定成分在基因敲除小鼠诱发异常性疼痛中的作用,我们建立了基因敲除小鼠坐骨神经部分结扎的方法,并获得了以下结果:环氧化酶(COX)是PG产生的限速酶。虽然考克斯-1是组成型,但考克斯-2是诱导型,并被认为是炎症中PG产生的原因。1)尽管在治疗后1周诱导了异常性疼痛,但在考克斯-2^<-/->小鼠中观察到异常性疼痛,表明考克斯-2不参与异常性疼痛的诱导。2)考克斯-1选择性抑制剂,而不是考克斯-2选择性抑制剂,减轻坐骨神经损伤引起的疼痛反应。3)虽然在iNOS^<-/->小鼠中观察到异常性疼痛,但在NMDA^<-/->小鼠中疼痛反应消失。这些结果表明,由PGE 2激活的谷氨酸兴奋性传递在坐骨神经损伤后疼痛的诱导和维持中起着关键作用。为了阐明异常性疼痛的诱导和维持,我们将扩大坐骨神经损伤模型的研究,并将其与i. t. PG异常性疼痛模型。

项目成果

期刊论文数量(48)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Minami,T.: "Characterization of nociceptin/orphanin FQ-induced pain responses in conscius mice : neonatal capsaicin treatment and NMDA receptor GluRε subunit knockout mice."Neuroscience. 97. 133-142 (2000)
Minami, T.:“有意识小鼠中伤害感受肽/孤啡肽 FQ 诱导的疼痛反应的表征:新生辣椒素治疗和 NMDA 受体 GluRε 亚基敲除小鼠。神经科学”。
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    0
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Minami,M.: "Involvement of primary afferent C-fibers in touch-evoked pain (allodynia) induced by prostaglandin E_2"Eur.J.Neurosci.. 11. 1849-1856 (1999)
Minami,M.:“初级传入 C 纤维参与前列腺素 E_2 诱导的触摸诱发疼痛(异常性疼痛)”Eur.J.Neurosci.. 11. 1849-1856 (1999)
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    0
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Ito, S.: "Central role of nociceptin/orphanin FQ and nocistatin: allodynia as a model of neural plasticity."Progress Brain Res. -Nervous system plasticity and chronic pain.. (in press). (2000)
Ito, S.:“伤害感受肽/孤啡肽 FQ 和伤害抑制素的核心作用:异常性疼痛作为神经可塑性模型。”Progress Brain Res。
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
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  • 通讯作者:
Ito,S.: "Central roles of nociceptin/orphanin FQ and nocistatin : allodynia as a model of neural plasticity."Prog.Brain Res.. 129. 205-218 (2000)
Ito,S.:“伤害感受肽/孤啡肽 FQ 和伤害抑制素的核心作用:异常性疼痛作为神经可塑性模型。”Prog.Brain Res.. 129. 205-218 (2000)
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  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Nakano,H.: "Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ."J.Pharmacol.Exp.Ther.. 292. 331-336 (2000)
Nakano, H.:“鞘内注射诺西他汀与伤害感受汀/孤啡宁 FQ 相比,对小鼠福尔马林引起的疼痛的影响。”J.Pharmacol.Exp.Ther.. 292. 331-336 (2000)
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ITO Seiji其他文献

ITO Seiji的其他文献

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{{ truncateString('ITO Seiji', 18)}}的其他基金

Isolation of circulating tumor cells (CTC) and peritoneal tumor cells (PTC) by cytology-based filtration platform and its application to monitoring therapeutic effect
基于细胞学的过滤平台分离循环肿瘤细胞(CTC)和腹膜肿瘤细胞(PTC)及其在监测疗效中的应用
  • 批准号:
    16K10524
  • 财政年份:
    2016
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
3D analysis of functional neural network of sensory input and output in the spinal cord by use of transgenic mice expressing fluorescent proteins
利用表达荧光蛋白的转基因小鼠对脊髓感觉输入和输出的功能神经网络进行 3D 分析
  • 批准号:
    25293137
  • 财政年份:
    2013
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Detection of free intraperitoneal/circulating tumor cells and possible selection of chemosensitive patientsfor neoadjuvant chemotherapy using gene expression analysis for gastric cancer.
使用胃癌基因表达分析检测游离腹膜内/循环肿瘤细胞,并可能选择化疗敏感患者进行新辅助化疗。
  • 批准号:
    25462043
  • 财政年份:
    2013
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study on gate control theory of pain by two-photon microsucopy using gene-engineered mice.
双光子显微基因工程小鼠疼痛门控理论研究
  • 批准号:
    23659322
  • 财政年份:
    2011
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Detection of free intraperitoneal cancer cells and chemosensitivity testing using gene expression analysis for gastric cancer patients
胃癌患者腹膜内游离癌细胞的检测及基因表达分析的化疗敏感性试验
  • 批准号:
    22591473
  • 财政年份:
    2010
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Intracellular signal transduction of chronic pain in the spinal cord and tempospatial analysis of intercellular bioactive substances
脊髓慢性疼痛的细胞内信号转导及细胞间生物活性物质的时空分析
  • 批准号:
    22390063
  • 财政年份:
    2010
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Systematic study on the mechanism of generation, maintenance and recognition of neuropathic pain, a model of neural plasticity
神经病理性疼痛产生、维持和识别机制的系统研究,神经可塑性模型
  • 批准号:
    17109005
  • 财政年份:
    2005
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (S)
Functional analysis of protein complex involved in neuropathic pain by proteomics
通过蛋白质组学对参与神经病理性疼痛的蛋白质复合物进行功能分析
  • 批准号:
    15390109
  • 财政年份:
    2003
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Studies on neural regeneration and reorganization of neural circuits in neuropathic pain
神经病理性疼痛的神经再生和神经回路重组的研究
  • 批准号:
    13470039
  • 财政年份:
    2001
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Cloning of nocistatin receptor and development of new aanalgesics
诺西他汀受体的克隆及新型镇痛药的开发
  • 批准号:
    11558093
  • 财政年份:
    1999
  • 资助金额:
    $ 2.69万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).

相似国自然基金

钠激活钾通道(KNa)在神经损伤引起的痛觉超敏(allodynia)中的作用
  • 批准号:
    81300952
  • 批准年份:
    2013
  • 资助金额:
    23.0 万元
  • 项目类别:
    青年科学基金项目

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    10856753
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    10603436
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
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