Mechanisms of Central Sensitization

中枢敏化机制

基本信息

  • 批准号:
    10188656
  • 负责人:
  • 金额:
    $ 51.14万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-04-01 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

Abstract Chronic pain represents an immense clinical problem, with over 100 million Americans afflicted and an annual price tag exceeding half a trillion dollars, according to a recent report from the Institute of Medicine. Studies in our lab are designed to identify molecular, cellular, and circuit mechanisms of sensitization in pain pathways with the goal of identifying novel targets for analgesic intervention. Studies performed in our lab previously identified a critical signaling cascade in neurons of the central nucleus of the amygdala (CeA) that underlies central pain sensitization. This pathway is initiated by metabotropic glutamate receptor subtype 5 (mGlu5) activation of extracellular signal-regulated kinase/ERK signaling, leading to increased firing of CeA neurons. This increase in excitability likely contributes to central sensitization associated with persistent pain. Our prior work, and that of several other groups, suggests that neurons in the CeA represent a critical node of neuromodulation underlying the development of chronic pain. An important finding from our prior studies was that this maladaptive plasticity in the CeA leading to persistent pain sensitization is specific to the right hemisphere. That is, no matter the sight of the injury, plasticity in the right (and not left) CeA was responsible for bilateral pain hypersensitivity. Furthermore, manipulation of neural activity only in the right CeA was found to produce bilateral pain sensitization. The mechanisms generating this hemispheric lateralization are completely unknown. In the present application, we will conduct a series of studies aimed at understanding the circuit context of CeA neurons that are activated by acute pain sensitization. We will perform studies aimed at identifying critical inputs, the type of plasticity that occurs at these synapses, and the major outputs of pain-responsive CeA neurons. We will test whether CeA neurons activated in the context of pain sensitization are necessary and sufficient for the development of pain sensitization, ongoing pain and comorbid disorders. By specifically targeting pain- activated neurons in this study, we may be able to determine if they possess unique neurochemical properties that represent novel therapeutic targets, or genetic signatures that would enable future studies to more precisely determine their function. In vivo 2-photon imaging and microendoscope cameras will be used to monitor activity of these neurons using genetically-encoded Ca2+ sensors, over days to weeks, to determine how the properties of these neurons change during the transition from acute to persistent pain. We will ask whether the population of neurons responsive to heat, cold, or touch change over time, and whether altered activity of these neurons in persistent pain conditions can be normalized using treatments that reduce pain or comorbid anxiety. These studies employ a host of modern techniques including advanced viral tracing, genetic mapping, in vivo calcium imaging, and optogenetic approaches, together with technologies developed in our lab for wireless optogenetic studies to address these important questions.
摘要

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)

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Robert W Gereau其他文献

Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-κB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine
  • DOI:
    10.1186/1744-8069-2-20
  • 发表时间:
    2006-06-09
  • 期刊:
  • 影响因子:
    2.800
  • 作者:
    Santina Chiechio;Agata Copani;Laura De Petris;Maria Elena P Morales;Ferdinando Nicoletti;Robert W Gereau
  • 通讯作者:
    Robert W Gereau

Robert W Gereau的其他文献

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{{ truncateString('Robert W Gereau', 18)}}的其他基金

Functional and genetic characterization of human DRG and spinal cord at single cell resolution
单细胞分辨率下人类 DRG 和脊髓的功能和遗传特征
  • 批准号:
    10593847
  • 财政年份:
    2022
  • 资助金额:
    $ 51.14万
  • 项目类别:
Core A: Administration
核心A:管理
  • 批准号:
    10593844
  • 财政年份:
    2022
  • 资助金额:
    $ 51.14万
  • 项目类别:
INTERCEPT: Integrated Research Center for human Pain Tissues
截取:人类疼痛组织综合研究中心
  • 批准号:
    10707405
  • 财政年份:
    2022
  • 资助金额:
    $ 51.14万
  • 项目类别:
Core A: Administration
核心A:管理
  • 批准号:
    10707406
  • 财政年份:
    2022
  • 资助金额:
    $ 51.14万
  • 项目类别:
Functional and genetic characterization of human DRG and spinal cord at single cell resolution
单细胞分辨率下人类 DRG 和脊髓的功能和遗传特征
  • 批准号:
    10707419
  • 财政年份:
    2022
  • 资助金额:
    $ 51.14万
  • 项目类别:
INTERCEPT: Integrated Research Center for human Pain Tissues
截取:人类疼痛组织综合研究中心
  • 批准号:
    10593843
  • 财政年份:
    2022
  • 资助金额:
    $ 51.14万
  • 项目类别:
Mechanisms of Central Sensitization
中枢敏化机制
  • 批准号:
    10202941
  • 财政年份:
    2020
  • 资助金额:
    $ 51.14万
  • 项目类别:
Development of an implantable closed-loop system for delivery of naloxone for the prevention of opioid-related overdose deaths
开发用于输送纳洛酮的植入式闭环系统,以预防阿片类药物相关的过量死亡
  • 批准号:
    10022117
  • 财政年份:
    2019
  • 资助金额:
    $ 51.14万
  • 项目类别:
Development of an implantable closed-loop system for delivery of naloxone for the prevention of opioid-related overdose deaths
开发用于输送纳洛酮的植入式闭环系统,以预防阿片类药物相关的过量死亡
  • 批准号:
    10456452
  • 财政年份:
    2019
  • 资助金额:
    $ 51.14万
  • 项目类别:
Development of an implantable closed-loop system for delivery of naloxone for the prevention of opioid-related overdose deaths
开发用于输送纳洛酮的植入式闭环系统,以预防阿片类药物相关的过量死亡
  • 批准号:
    9902945
  • 财政年份:
    2019
  • 资助金额:
    $ 51.14万
  • 项目类别:

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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:
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婴幼儿急性疼痛治疗的临床结果评估 (COA APTIC)
  • 批准号:
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    $ 51.14万
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  • 批准号:
    10740796
  • 财政年份:
    2023
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Predicting Pediatric Sickle Cell Disease Acute Pain Using Mathematical Models Based on mHealth Data
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    2022
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    $ 51.14万
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Non-Contingent Acute Pain Stress Drives Analgesic Protection in Rats.
非偶然急性疼痛应激驱动大鼠镇痛保护。
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    575854-2022
  • 财政年份:
    2022
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    $ 51.14万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Prefrontal Cortex Hemodynamic Responses to Mindfulness Meditation and Acute Pain
前额皮质血流动力学对正念冥想和急性疼痛的反应
  • 批准号:
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  • 财政年份:
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  • 项目类别:
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监测新生儿长期急性疼痛的多模式方法
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  • 财政年份:
    2020
  • 资助金额:
    $ 51.14万
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  • 批准号:
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    $ 51.14万
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监测新生儿长期急性疼痛的多模式方法
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