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
- 来源:
- 关键词:Absence of pain sensationAcupuncture TherapyAcute PainAgeAgingAlcohol consumptionAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAnalgesicsAnteriorArousalBiological MarkersBrainCardiovascular DiseasesCardiovascular systemChronicChronic stressComplementary HealthDataDiabetes MellitusDrainage procedureEicosapentaenoic AcidExerciseGoalsHeavy DrinkingHyperalgesiaHypersensitivityHypertensionImmune systemInflammationIntegrative MedicineInterventionLightLymphatic SystemLymphatic clearanceMedicalMelatoninMetabolicMetabolic syndromeMicrodialysisMind-Body InterventionModelingModernizationMusNeural PathwaysNorepinephrineOmega-3 Fatty AcidsOperating SystemPainPathologyPathway interactionsPeripheralPharmacologyPhenotypeProcessResearch PersonnelRestSeveritiesSleepSleep DeprivationSleep disturbancesStressSystemTechniquesTemperatureTestingTherapeuticTimeTraumatic Brain InjuryTreatment EfficacyWakefulnessWorkallodyniabasebody-mindchronic neuropathic painchronic painchronic pain managementchronic pain patientcingulate cortexcircadiancytokineexperienceglymphatic clearanceglymphatic flowglymphatic functionglymphatic systemimprovedimprovement on sleepinterestmouse modelnerve injuryneuronal excitabilitypain modelpain perceptionpain reductionpain reliefpain sensitivitypainful neuropathypatient populationpoor sleeppre-clinicalresponsesleep qualitysolutetargeted treatmenttreatment effectwasting
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
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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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
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:
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:
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