The glymphatic system at the crossroad of integrative health approaches inchronic pain

处于综合健康十字路口的类淋巴系统接近慢性疼痛

基本信息

  • 批准号:
    10453615
  • 负责人:
  • 金额:
    $ 54.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-08-01 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

Abstract: The glymphatic system is a network of perivascular spaces that function as a waste clearance system, analogous to the peripheral lymphatic system. Reduced glymphatic function has been a hallmark observation in aging as well as models of Alzheimer's disease, diabetes, hypertension, traumatic brain injury, excess alcohol intake, and chronic unpredictable stress. Preliminary data shows that acute and chronic pain, and one night of light all suppressed glymphatic function. This application will use the murine sparse nerve injury (SNI) model to understand how the brain responds to chronic neuropathic pain. Sleep complaints are prevalent in chronic pain patients, and chronic sleep restriction increases pain sensitivity in mice. Norepinephrine (NE), which disrupts sleep and is released in stressful conditions, suppresses glymphatic function. We hypothesize that increase NE levels in SNI reduce glymphatic function, triggering cytokine accumulation, neuronal excitability, sleep disruption and pain sensitization in a feedforward loop (Aim 1). Traditional analgesics have been shown to relieve pain in models of chronic pain. Our preliminary data show that the same agents restore glymphatic function in SNI mice with no effect on glymphatic functions in control mice. We hypothesize that reducing the severity of pain via analgesia improves glymphatic function by reducing NE levels, which in turn reduces cytokine accumulation and excitability and improves sleep quality (Aim 2.1). Yet, efficacy of modern pharmacology is variable in the patient population, suggesting that while modulation of neural pathways is partially effective, pathology remains. We hypothesize that neuropathic pain induces a CNS maladaptive response involving reduced glymphatic flow, inflammation and waste accumulation. Because both natural and mind-body interventions target multiple facets of glymphatic disruption (sleep, inflammation, cardiovascular disease), we hypothesize that natural supplements (melatonin and eicosapentaenoic acid (an ω-3 fatty acid)) and mind-body interventions (voluntary exercise, improved sleep, and acupuncture) will improve glymphatic disruption in chronic pain (Aims 2.2 and 2.3). The timing of treatment is critical, because the circadian system is integrated into every process in the body including the glymphatic system, the immune system, and chronic pain. We propose that targeting therapeutics to reinforce the rhythm in glymphatic function and clearance will optimize the effect of treatment which can be quantified as an additional decrease in cytokine accumulation and hyperalgesia in SNI (Aim 3). We will time sleep improvements via increased temperature, voluntary exercise, melatonin, and acupuncture, to the endogenous rhythm of CSF distribution - high glymphatic clearance during rest, and low during wakefulness. Aim 3 is unique in that it tests whether efficacy of mind-body therapies, in improving glymphatic function and reducing pain sensitivity, can change based on when during the day they are administered. Overall, this application aims to define whether glymphatic activity may serve as a target for complementary therapeutic approaches and also as a biomarker establishing the efficacy of treatment.
摘要:淋巴系统是一个血管周围空间网络,具有废物清除系统的功能。

项目成果

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Maiken Nedergaard其他文献

Maiken Nedergaard的其他文献

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{{ truncateString('Maiken Nedergaard', 18)}}的其他基金

Administrative Core
行政核心
  • 批准号:
    10673148
  • 财政年份:
    2022
  • 资助金额:
    $ 54.98万
  • 项目类别:
Project 2: Periarterial CSF pumping: Dependence on state of brain activity
项目 2:动脉周围脑脊液泵送:取决于大脑活动状态
  • 批准号:
    10673161
  • 财政年份:
    2022
  • 资助金额:
    $ 54.98万
  • 项目类别:
Administrative Core
行政核心
  • 批准号:
    10516498
  • 财政年份:
    2022
  • 资助金额:
    $ 54.98万
  • 项目类别:
Project 2: Periarterial CSF pumping: Dependence on state of brain activity
项目 2:动脉周围脑脊液泵送:取决于大脑活动状态
  • 批准号:
    10516502
  • 财政年份:
    2022
  • 资助金额:
    $ 54.98万
  • 项目类别:
Does suppression of glymphatic flow explain why chronic neuropathic pain elevates the risk of developing Alzheimer-like dementia?
类淋巴液流的抑制是否可以解释为什么慢性神经性疼痛会增加患阿尔茨海默样痴呆的风险?
  • 批准号:
    10711478
  • 财政年份:
    2021
  • 资助金额:
    $ 54.98万
  • 项目类别:
The glymphatic system at the crossroad of integrative health approaches inchronic pain
处于综合健康十字路口的类淋巴系统接近慢性疼痛
  • 批准号:
    10626911
  • 财政年份:
    2021
  • 资助金额:
    $ 54.98万
  • 项目类别:
Does suppression of glymphatic flow explain why chronic neuropathic pain elevates the risk of developing Alzheimer-like dementia?
类淋巴液流的抑制是否可以解释为什么慢性神经性疼痛会增加患阿尔茨海默样痴呆的风险?
  • 批准号:
    10834414
  • 财政年份:
    2021
  • 资助金额:
    $ 54.98万
  • 项目类别:
The glymphatic system at the crossroad of integrative health approaches inchronic pain
处于综合健康十字路口的类淋巴系统接近慢性疼痛
  • 批准号:
    10213385
  • 财政年份:
    2021
  • 资助金额:
    $ 54.98万
  • 项目类别:
Para-Vascular Basis of Small Vessel Disease
小血管疾病的血管旁基础
  • 批准号:
    9263196
  • 财政年份:
    2016
  • 资助金额:
    $ 54.98万
  • 项目类别:
Para-Vascular Basis of Small Vessel Disease
小血管疾病的血管旁基础
  • 批准号:
    9756479
  • 财政年份:
    2016
  • 资助金额:
    $ 54.98万
  • 项目类别:

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针灸治疗血液透析患者疲劳——自主神经系统双盲RCT研究。
  • 批准号:
    17K09291
  • 财政年份:
    2017
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支持针灸治疗心理社会方面的基于大脑的机制的优化——一项超扫描功能磁共振成像研究
  • 批准号:
    9999445
  • 财政年份:
    2016
  • 资助金额:
    $ 54.98万
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Optimization of brain-based mechanisms supporting psychosocial aspects of acupuncture therapy - a hyperscanning fMRI study
支持针灸治疗心理社会方面的基于大脑的机制的优化——一项超扫描功能磁共振成像研究
  • 批准号:
    9348587
  • 财政年份:
    2016
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    $ 54.98万
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Establishment of prevention method for sarcopenia in elderly by acupuncture therapy
针灸预防老年肌少症方法的建立
  • 批准号:
    15K08916
  • 财政年份:
    2015
  • 资助金额:
    $ 54.98万
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针灸治疗肌肉萎缩的临床应用基础研究
  • 批准号:
    26870555
  • 财政年份:
    2014
  • 资助金额:
    $ 54.98万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
  • 批准号:
    8518241
  • 财政年份:
    2009
  • 资助金额:
    $ 54.98万
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A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
  • 批准号:
    8294798
  • 财政年份:
    2009
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    $ 54.98万
  • 项目类别:
A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
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    2009
  • 资助金额:
    $ 54.98万
  • 项目类别:
A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
  • 批准号:
    8111166
  • 财政年份:
    2009
  • 资助金额:
    $ 54.98万
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A Method for Evaluating Acupuncture Therapy in Pain Management
评估针灸治疗疼痛的方法
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    7845141
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