The role of neuroimmune interactions in the pathogenesis of chronic pain

神经免疫相互作用在慢性疼痛发病机制中的作用

基本信息

  • 批准号:
    10451784
  • 负责人:
  • 金额:
    $ 58.6万
  • 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:
    2018-09-10 至 2024-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract Nerve injury-induced neuropathic pain is a major health problem with limited treatment. Insufficient understanding of this disorder at the level of neural circuits impedes the development of effective therapies. The activation of the immune system and neuronal alterations in the somatosensory pathway are known to be critical for the genesis of neuropathic pain. However, how immune cells interact with neurons after peripheral nerve injury and contribute to persistent and intense pain sensation remains largely elusive. Our recent studies have shown that monocytes and microglia synergistically promote the development of neuropathic pain symptoms. We have also developed novel approaches for imaging and manipulating neurons and nonneuronal cells (e.g. monocytes, microglia and astrocytes) in the pain pathway, from peripheral dorsal root ganglia (DRG), the primary somatosensory cortex (S1) to anterior cingulate cortex (ACC) in the awake, behaving mice. In our preliminary studies, we have found that following peripheral nerve injury, DRG sensory neuron activities undergo rapid and transient increases whereas pyramidal neuronal activities in the S1 and ACC rise progressively and remain elevated under chronic pain states. Moreover, selective depletion of microglial cytokine TNF-alpha production attenuates pain hypersensitivity after nerve injury. Based on these findings, we hypothesize that the interactions among peripheral monocytes, brain microglia and astrocytes play critical roles in the emergence of hyperactive neurons in the cortex during the transition from acute to chronic pain. In this application, we will test this hypothesis by combining in vivo two-photon imaging of synapse structure and neuronal activity, genetic manipulation of molecularly defined cell types in cortical circuitry, as well as behavioral testing for sensory and affective pain symptoms. Specifically, in Aim 1, we will characterize the sequential changes of neuronal activities in the pain circuits after peripheral nerve injury. This will test the hypothesis that dynamic changes in pain circuits occur progressively from the DRG to the cortex and that persistent neuronal hyperactivity emerging in S1 and ACC is critical for the induction of chronic neuropathic pain. In Aim 2, we will combine in vivo calcium imaging with in vivo cell depletion and bone marrow chimeric strategies to investigate the synergistic roles of monocytes and microglia in the emergence of persistent cortical hyperactivity. In Aim 3, we will test the hypothesis that monocytes/microglia promote nerve injury- induced neuronal hyperactivity via proinflammatory cytokines and astrocytes in the cortex. Together, our proposed research will significantly expand the knowledge on the contribution of neuroimmune interactions to the development of neuropathic pain. They will also help identify immune cells as novel targets for the development of effective pain therapies.
项目总结/文摘

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A mesocortical glutamatergic pathway modulates neuropathic pain independent of dopamine co-release.
  • DOI:
    10.1038/s41467-024-45035-2
  • 发表时间:
    2024-01-20
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Li, Miao;Yang, Guang
  • 通讯作者:
    Yang, Guang
Activation of VIP interneurons in the prefrontal cortex ameliorates neuropathic pain aversiveness.
  • DOI:
    10.1016/j.celrep.2022.111333
  • 发表时间:
    2022-09-13
  • 期刊:
  • 影响因子:
    8.8
  • 作者:
    Li, Miao;Zhou, Hang;Teng, Sasa;Yang, Guang
  • 通讯作者:
    Yang, Guang
Synchronized activity of sensory neurons initiates cortical synchrony in a model of neuropathic pain.
  • DOI:
    10.1038/s41467-023-36093-z
  • 发表时间:
    2023-02-08
  • 期刊:
  • 影响因子:
    16.6
  • 作者:
    Chen, Chao;Sun, Linlin;Adler, Avital;Zhou, Hang;Zhang, Licheng;Zhang, Lihai;Deng, Junhao;Bai, Yang;Zhang, Jinhui;Yang, Guang;Gan, Wen-Biao;Tang, Peifu
  • 通讯作者:
    Tang, Peifu
A sleep-active basalocortical pathway crucial for generation and maintenance of chronic pain.
睡眠活跃的基底层途径对于慢性疼痛的产生和维持至关重要。
  • DOI:
    10.1038/s41593-022-01250-y
  • 发表时间:
    2023-03
  • 期刊:
  • 影响因子:
    25
  • 作者:
    Zhou, Hang;Li, Miao;Zhao, Ruohe;Sun, Linlin;Yang, Guang
  • 通讯作者:
    Yang, Guang
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MOSES VICTOR CHAO其他文献

MOSES VICTOR CHAO的其他文献

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{{ truncateString('MOSES VICTOR CHAO', 18)}}的其他基金

Attenuation of neuroinflammation and Alzheimer’s disease pathology by disrupting LXRα phosphorylation
通过破坏 LXRα 磷酸化来减轻神经炎症和阿尔茨海默病病理学
  • 批准号:
    10285124
  • 财政年份:
    2021
  • 资助金额:
    $ 58.6万
  • 项目类别:
Attenuation of neuroinflammation and Alzheimer’s disease pathology by disrupting LXRα phosphorylation
通过破坏 LXRα 磷酸化来减轻神经炎症和阿尔茨海默病病理学
  • 批准号:
    10460595
  • 财政年份:
    2021
  • 资助金额:
    $ 58.6万
  • 项目类别:
Targets of Oxytocin Receptor Signaling
催产素受体信号传导的靶点
  • 批准号:
    9901580
  • 财政年份:
    2019
  • 资助金额:
    $ 58.6万
  • 项目类别:
Targets of Oxytocin Receptor Signaling
催产素受体信号传导的靶标
  • 批准号:
    10569535
  • 财政年份:
    2019
  • 资助金额:
    $ 58.6万
  • 项目类别:
Targets of Oxytocin Receptor Signaling
催产素受体信号传导的靶标
  • 批准号:
    10348686
  • 财政年份:
    2019
  • 资助金额:
    $ 58.6万
  • 项目类别:
Diverse Neuroscientists: Doctoral Training Series (DeNDriTeS)
多元化的神经科学家:博士培训系列 (DeNDriTeS)
  • 批准号:
    10447210
  • 财政年份:
    2018
  • 资助金额:
    $ 58.6万
  • 项目类别:
Molecular Tools Core
分子工具核心
  • 批准号:
    10705993
  • 财政年份:
    2018
  • 资助金额:
    $ 58.6万
  • 项目类别:
Antibody Core
抗体核心
  • 批准号:
    10220154
  • 财政年份:
    2018
  • 资助金额:
    $ 58.6万
  • 项目类别:
Diverse Neuroscientists: Doctoral Training Series (DeNDriTeS)
多元化的神经科学家:博士培训系列 (DeNDriTeS)
  • 批准号:
    10199068
  • 财政年份:
    2018
  • 资助金额:
    $ 58.6万
  • 项目类别:
Antibody Core
抗体核心
  • 批准号:
    10438590
  • 财政年份:
    2018
  • 资助金额:
    $ 58.6万
  • 项目类别:

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社交媒体上的情感病毒传播:文化和理想情感的作用
  • 批准号:
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  • 批准号:
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  • 财政年份:
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Influence of Physical Activity on Daily Positive Affect & Affective Neural Activity in Preschoolers
体力活动对日常积极影响的影响
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    10475608
  • 财政年份:
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    2015
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