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.
疼痛的感觉为伤害的发生提供了有用的警告。然而,在长期炎症、手术后和神经损伤等病理条件下,外周的伤害性感受器被激活,产生自发性疼痛、痛觉过敏和触觉疼痛(超敏)。我们已经证实:1)鞘内注射前列腺素E_2和前列腺素F_2α可引起痛觉异常;2)辣椒素敏感和不敏感途径参与了痛觉异常的诱导;3)前列腺素可通过生物医学途径从突触末梢释放谷氨酸,激活→受体→,从而产生痛觉过敏。4)PGD2可阻断PGE2诱发的痛觉超敏。为了阐明特定成分在基因敲除小鼠诱发痛觉过敏中的作用,我们建立了部分坐骨神经结扎的基因敲除小鼠模型,并获得了以下结果。环氧合酶(COXS)是PG产生的限速酶。COX-1是一种结构性形式,而COX-2是一种诱导形式,被认为是炎症中PG产生的原因。1)虽然在治疗1周后出现了痛觉异常,但在COX-2^&lt;-/-&gt;小鼠中观察到了痛觉异常,提示COX-2不参与痛觉异常的诱导。2)COX-1选择性抑制剂可减轻坐骨神经损伤所致的疼痛反应,而COX-2选择性抑制剂无此作用。3)当iNOS^&lt;-/-&gt;小鼠出现痛觉超敏时,NMDA^&lt;-/-&gt;小鼠的痛觉反应消失。这些结果表明,PGE2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关键作用。为了阐明痛觉异常的诱发和维持,我们将扩展坐骨神经损伤模型的研究,并将其与I.T.PG痛觉超敏模型。

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”。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
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)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
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:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 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)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 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)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

ITO Seiji其他文献

ITO Seiji的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ 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

相似海外基金

Elucidating causal mechanisms of ethanol-induced analgesia in BXD recombinant inbred mouse lines
阐明 BXD 重组近交系小鼠乙醇诱导镇痛的因果机制
  • 批准号:
    10825737
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Selective actin remodeling of sensory neurons for acute pain management
感觉神经元的选择性肌动蛋白重塑用于急性疼痛管理
  • 批准号:
    10603436
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
The role of meningeal immune cells in the efficacy of CGRP-based migraine therapies
脑膜免疫细胞在 CGRP 偏头痛疗法疗效中的作用
  • 批准号:
    10604482
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Developing multitarget enzyme inhibitors as safe and effective anti-migraine treatments
开发多靶点酶抑制剂作为安全有效的抗偏头痛治疗方法
  • 批准号:
    10714658
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Project #1 Single-soma RNA-seq and spatial transcriptomics of human TGs
项目
  • 批准号:
    10806547
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Project #3 In vivo microneurography recordings of sensory afferents
项目
  • 批准号:
    10806549
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Immune mechanisms of pain of the IL-23IL-17 Axis in Inflammatory Arthritis
炎症性关节炎中 IL-23IL-17 轴疼痛的免疫机制
  • 批准号:
    10861492
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Intra-Articular Drug Delivery Modulating Immune Cells in Inflammatory Joint Disease
关节内药物递送调节炎症性关节疾病中的免疫细胞
  • 批准号:
    10856753
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Mitochondrial regulation of nociceptor function
伤害感受器功能的线粒体调节
  • 批准号:
    10644865
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
Evaluation of the Role of Macrophage Migratory Inhibitory Factor (MIF) in mediating Stem Cell Analgesia in a Model of Orofacial Pain
评估巨噬细胞迁移抑制因子(MIF)在口面部疼痛模型中介导干细胞镇痛的作用
  • 批准号:
    10585412
  • 财政年份:
    2023
  • 资助金额:
    $ 2.69万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了