Molecular Pain Mechanisms

分子疼痛机制

基本信息

  • 批准号:
    7467338
  • 负责人:
  • 金额:
    $ 28.57万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2007
  • 资助国家:
    美国
  • 起止时间:
    2007-07-15 至 2011-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): We propose to study a novel mechanism by which sensory neurons detect noxious stimuli. The ability to detect noxious stimuli is critical to survival, but can also be the source of unwanted pain. Injurious chemical, thermal and mechanical stimuli are transduced by a variety of G-protein coupled receptors and ion channels expressed in nociceptive sensory neurons. The signaling pathways in these neurons are undoubtedly complex, but deciphering these pathways promises the potential for improved treatment of pain-the most frequently cited health-care concern. One newly identified mode of noxious signaling occurs via the electrostatic charge of cations. Extracellular cations and polyamines can directly sensitize and gate the capsaicin receptor TRPV1, an ion channel essential for the development of inflammatory hyperalgesia. An important question arising from this observation is whether basic peptides can similarly modulate the function of TRPV1 and thereby regulate sensory nerve excitability. Immune and epithelial cells secrete an array of highly charged, cationic proteins and peptides. Importantly, levels of these cations are markedly elevated in inflamed tissue, however despite this observation; their effects on sensory nerve function have barely been explored. We hypothesize that polycations and cationic peptides can regulate the excitability of nociceptors through the modulation of TRPV1. We will test this innovative hypothesis using a combination of robust electrophysiological and biochemical methodologies: In Aim 1 we will determine the activation and sensitization of TRPV1 by several inflammatory cationic peptides/proteins. In Aim 2 we will explore the ability of polyamines and cationic peptides to trigger neuropeptide secretion from peripheral and central terminals of sensory nerve preparations. In Aim 3 we plan to identify nociceptive behaviors and pathology arising from cationic regulation of TRPV1.
描述(由申请人提供):我们提出研究一种新的机制,通过这种机制,感觉神经元检测伤害性刺激。检测有害刺激的能力对生存至关重要,但也可能是不必要的疼痛的来源。伤害性化学、热和机械刺激通过伤害性感觉神经元中表达的多种G蛋白偶联受体和离子通道转导。这些神经元中的信号通路无疑是复杂的,但破译这些通路有望改善疼痛治疗的潜力-最常被引用的医疗保健问题。一种新发现的有害信号模式是通过阳离子的静电荷发生的。细胞外阳离子和多胺可以直接敏化和门控辣椒素受体TRPV 1,一种对炎症性痛觉过敏的发展至关重要的离子通道。从这一观察中产生的一个重要问题是碱性肽是否可以类似地调节TRPV 1的功能,从而调节感觉神经的兴奋性。免疫和上皮细胞分泌一系列高度带电的阳离子蛋白质和肽。重要的是,这些阳离子的水平在发炎组织中显著升高,然而,尽管有这种观察结果;它们对感觉神经功能的影响几乎没有被探索过。我们推测聚阳离子和阳离子肽可以通过调节TRPV 1来调节伤害感受器的兴奋性。我们将使用强大的电生理学和生物化学方法的组合来测试这一创新假设:在目标1中,我们将确定几种炎性阳离子肽/蛋白对TRPV 1的激活和致敏作用。在目标2中,我们将探讨多胺和阳离子肽触发感觉神经制备物的外周和中枢末端的神经肽分泌的能力。在目标3中,我们计划确定TRPV 1的阳离子调节引起的伤害性行为和病理学。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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

{{ 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 }}

GERARD P AHERN其他文献

GERARD P AHERN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('GERARD P AHERN', 18)}}的其他基金

TRPV1 and the regulation of arterial tone
TRPV1 和动脉张力的调节
  • 批准号:
    10299144
  • 财政年份:
    2021
  • 资助金额:
    $ 28.57万
  • 项目类别:
TRPV1 and the regulation of arterial tone
TRPV1 和动脉张力的调节
  • 批准号:
    10630275
  • 财政年份:
    2021
  • 资助金额:
    $ 28.57万
  • 项目类别:
TRPV1 and the regulation of arterial tone
TRPV1 和动脉张力的调节
  • 批准号:
    10461913
  • 财政年份:
    2021
  • 资助金额:
    $ 28.57万
  • 项目类别:
Nociceptive Innervation and Receptors in the Bladder
膀胱中的伤害性神经支配和感受器
  • 批准号:
    8636843
  • 财政年份:
    2013
  • 资助金额:
    $ 28.57万
  • 项目类别:
TRPA1 and General Anesthetics
TRPA1 和全身麻醉剂
  • 批准号:
    8190901
  • 财政年份:
    2011
  • 资助金额:
    $ 28.57万
  • 项目类别:
TRPA1 and General Anesthetics
TRPA1 和全身麻醉剂
  • 批准号:
    8321455
  • 财政年份:
    2011
  • 资助金额:
    $ 28.57万
  • 项目类别:
Molecular Pain Mechanisms
分子疼痛机制
  • 批准号:
    7869550
  • 财政年份:
    2007
  • 资助金额:
    $ 28.57万
  • 项目类别:
Molecular Pain Mechanisms
分子疼痛机制
  • 批准号:
    7316440
  • 财政年份:
    2007
  • 资助金额:
    $ 28.57万
  • 项目类别:
Molecular Pain Mechanisms
分子疼痛机制
  • 批准号:
    7644993
  • 财政年份:
    2007
  • 资助金额:
    $ 28.57万
  • 项目类别:
Molecular Pain Mechanisms
分子疼痛机制
  • 批准号:
    7888151
  • 财政年份:
    2007
  • 资助金额:
    $ 28.57万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 28.57万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了