Mechanisms of Sleep Disruption Hyperalgesia
睡眠中断痛觉过敏的机制
基本信息
- 批准号:8471684
- 负责人:
- 金额:$ 53.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-06-01 至 2017-08-31
- 项目状态:已结题
- 来源:
- 关键词:Absence of pain sensationAcute PainAddressAmericanAnalgesicsAnimalsAttenuatedBehavioralBiologyCapsaicinCardiovascular DiseasesChronicChronic DiseaseClinicalComorbidityComplement Factor BComplexDataDevelopmentDimensionsEtiologyFunctional disorderGenetic TranscriptionGenomicsHealthcare SystemsHeatingHyperalgesiaImpairmentInflammationInflammatoryInterleukin-1 betaInterleukin-6InvestigationKnowledgeLaboratoriesLeadMaintenanceMeasuresMediatingMedicalMessenger RNAMethodsModelingMononuclearMorbidity - disease rateMorphineMusNeuronsNuclearOpiate AddictionOpioidPainPain ThresholdParticipantPathway interactionsPatternPharmaceutical PreparationsPlacebosPrevalencePreventionPrimary HyperalgesiasProcessProductionPsychoneuroimmunologyQuality of lifeRandomizedRefractoryRelative (related person)ResearchRiskRoleSecondary HyperalgesiasSensorySleepSleep DeprivationSleep DisordersSleep FragmentationsSleep disturbancesSleeplessnessSpinalSyndromeSystemTNF geneTestingTumor Necrosis Factor-alphaanaloganimal databasebiobehaviorchronic paincytokineendogenous opioidshuman subjectindexinginflammatory markerneurobehavioralnovelopioid misusepain inhibitionpreclinical studyprogramspublic health relevanceresearch studyresponsespontaneous paintranscription factor
项目摘要
DESCRIPTION (provided by applicant): Twenty percent of Americans suffer from chronic pain, a poorly understood condition that is refractory to treatment, severely limits quality of life, and is a tremendous burden on the healthcare system and the economy. Sleep disturbance is an equally ubiquitous problem and among the most common and disabling comorbidities associated with chronic pain. Sleep disturbance is not simply a consequence of pain, it substantially increases the risk of transitioning from acute pain to a chronic disorder. Although it is not known how sleep disturbance increases risk, preliminary evidence suggests that even partial sleep deprivation may cause hyperalgesia, i.e., enhanced responsivity to painful stimulation. Hyperalgesia is critical to the etiology and maintenance of chronic pain syndromes, but the complex biobehavioral factors that promote hyperalgesia are poorly understood. The mechanisms by which sleep disturbance promotes hyperalgesia have yet to be studied. We propose a novel research program to study the mechanisms of sleep disruption hyperalgesia (SD_HA). Addressing this knowledge gap has critical implications for the etiology, prevention and treatment of chronic pain. Pre-clinical studies and preliminary data from our groups implicate two possibly interrelated candidate mechanisms of major clinical import: 1) inflammation and 2) opioidergic antinociceptive system impairment. We have assembled an interdisciplinary team from Johns Hopkins and UCLA to conduct a controlled experiment in healthy human subjects to determine the role of inflammation in SD_HA and study the effects of sleep disruption and inflammation on opioid analgesia. We will employ a novel sleep disruption manipulation developed by our group that uses multiple, forced awakenings to mimic the pattern of sleep loss most commonly associated with pain and insomnia. Following undisturbed sleep and sleep disruption conditions, we will assess next-day hyperalgesia and analgesic response to either: (a) morphine or (b) placebo. Our specific aims are to: 1) examine the effects of experimental sleep disruption on spinal sensitization (secondary hyperalgesia) by evaluating laboratory pain responses in the heat-capsaicin pain model; 2) examine the effects of sleep disruption on opioid analgesia and 3) determine the effects of sleep disruption on genomic, cellular, and systemic markers of inflammation and characterize the role of inflammation on laboratory pain responses and opioid analgesia. We hypothesize that SD_HA and diminished opioid analgesia will be mediated by enhanced inflammation attributable to the sleep disruption manipulation. Focusing on genomic and cellular dimensions of the inflammatory cascade, opioidergic function and their interaction will lead to a better understanding of chronic pain pathophysiology and could have tremendous impact on the development of novel pain treatment and prevention methods. Findings will also have broad implications for problems such as opioid addiction and chronic medical conditions, such as cardiovascular disease in which inflammation contributes to morbidity and sleep disturbance is common.
描述(申请人提供):20%的美国人患有慢性疼痛,这是一种鲜为人知的疾病,难以治疗,严重限制了生活质量,是医疗保健系统和经济的巨大负担。睡眠障碍是一个同样无处不在的问题,也是与慢性疼痛有关的最常见和致残的共病之一。睡眠障碍不仅仅是疼痛的结果,它还大大增加了从急性疼痛过渡到慢性疾病的风险。尽管目前尚不清楚睡眠障碍是如何增加风险的,但初步证据表明,即使部分睡眠不足也可能导致痛觉过敏,即对痛苦刺激的反应增强。痛觉过敏对慢性疼痛综合征的病因和维持至关重要,但促进痛觉过敏的复杂生物行为因素却知之甚少。睡眠障碍促进痛觉过敏的机制还有待研究。我们提出了一个新的研究方案来研究睡眠中断痛觉过敏(SD_HA)的机制。解决这一知识差距对慢性疼痛的病因、预防和治疗具有重要意义。来自我们小组的临床前研究和初步数据表明,主要临床输入可能存在两种相互关联的候选机制:1)炎症和2)阿片能抗伤害性系统损害。我们组建了一个来自约翰·霍普金斯大学和加州大学洛杉矶分校的跨学科团队,在健康人身上进行了一项对照实验,以确定炎症在SD_HA中的作用,并研究睡眠中断和炎症对阿片类药物镇痛的影响。我们将采用我们团队开发的一种新颖的睡眠干扰操作,它使用多次强迫唤醒来模拟最常见的与疼痛和失眠有关的睡眠缺失模式。在未受干扰的睡眠和睡眠中断情况下,我们将评估第二天的痛觉过敏和对以下任一种药物的止痛反应:(A)吗啡或(B)安慰剂。我们的具体目标是:1)通过在热-辣椒素疼痛模型中评估实验室疼痛反应,检测实验性睡眠中断对脊髓敏化(继发性痛敏)的影响;2)检测睡眠中断对阿片类止痛的影响;3)确定睡眠中断对基因组、细胞和全身炎症标志物的影响,并表征炎症在实验室疼痛反应和阿片类镇痛中的作用。我们假设SD_HA和阿片类止痛减弱将由睡眠干扰操作引起的炎症增加所介导。关注炎症级联反应的基因组和细胞维度,阿片能功能及其相互作用将有助于更好地理解慢性疼痛的病理生理学,并可能对新的疼痛治疗和预防方法的发展产生巨大影响。这一发现也将对阿片成瘾和慢性医疗疾病等问题产生广泛影响,例如心血管疾病,炎症导致发病率,睡眠障碍很常见。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Michael R Irwin其他文献
Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity
睡眠健康:睡眠与先天免疫的相互调节
- DOI:
10.1038/npp.2016.148 - 发表时间:
2016-08-11 - 期刊:
- 影响因子:7.100
- 作者:
Michael R Irwin;Mark R Opp - 通讯作者:
Mark R Opp
Exploring the impact of a sleep app on sleep quality in a general population sample: a randomised controlled pilot trial (Preprint)
探索睡眠应用程序对一般人群样本睡眠质量的影响:随机对照试点试验(预印本)
- DOI:
10.2196/39554 - 发表时间:
2022 - 期刊:
- 影响因子:2.2
- 作者:
Bianca Tanya Armitage;Henry W W Potts;Michael R Irwin;Abi Fisher - 通讯作者:
Abi Fisher
In Sickness and in Health: The Co-Regulation of Inflammation and Social Behavior
《在疾病与健康中:炎症与社会行为的共同调节》
- DOI:
10.1038/npp.2016.141 - 发表时间:
2016-08-02 - 期刊:
- 影响因子:7.100
- 作者:
Naomi I Eisenberger;Mona Moieni;Tristen K Inagaki;Keely A Muscatell;Michael R Irwin - 通讯作者:
Michael R Irwin
Michael R Irwin的其他文献
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{{ truncateString('Michael R Irwin', 18)}}的其他基金
Mindfulness Meditation and Insomnia in Alzheimer Disease Caregivers: Inflammatory and Biological Aging Mechanisms
阿尔茨海默病护理人员的正念冥想和失眠:炎症和生物衰老机制
- 批准号:
9753113 - 财政年份:2017
- 资助金额:
$ 53.5万 - 项目类别:
Mindfulness Meditation and Insomnia in Alzheimer Disease Caregivers: Inflammatory and Biological Aging Mechanisms
阿尔茨海默病护理人员的正念冥想和失眠:炎症和生物衰老机制
- 批准号:
10200615 - 财政年份:2017
- 资助金额:
$ 53.5万 - 项目类别:
Mindfulness Meditation and Insomnia in Alzheimer Disease Caregivers: Inflammatory and Biological Aging Mechanisms
阿尔茨海默病护理人员的正念冥想和失眠:炎症和生物衰老机制
- 批准号:
9926024 - 财政年份:2017
- 资助金额:
$ 53.5万 - 项目类别:
Mindfulness Meditation and Insomnia in Alzheimer Disease Caregivers: Inflammatory and Biological Aging Mechanisms
阿尔茨海默病护理人员的正念冥想和失眠:炎症和生物衰老机制
- 批准号:
9364396 - 财政年份:2017
- 资助金额:
$ 53.5万 - 项目类别:
Biobehavioral Effects of Qigong for Prostate Cancer Survivors with Fatigue
气功对疲劳的前列腺癌幸存者的生物行为影响
- 批准号:
10064605 - 财政年份:2016
- 资助金额:
$ 53.5万 - 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
- 批准号:
9925164 - 财政年份:2016
- 资助金额:
$ 53.5万 - 项目类别:
Biobehavioral Effects of Qigong for Prostate Cancer Survivors with Fatigue
气功对疲劳的前列腺癌幸存者的生物行为影响
- 批准号:
9236404 - 财政年份:2016
- 资助金额:
$ 53.5万 - 项目类别:
Experimental Model of Depression in Aging: Insomnia, Inflammation, and Affect Mechanisms
衰老过程中抑郁症的实验模型:失眠、炎症和影响机制
- 批准号:
9345997 - 财政年份:2016
- 资助金额:
$ 53.5万 - 项目类别:
Sleep, Inflamation, and Depression Occurrence in Breast Cancer Survivors
乳腺癌幸存者的睡眠、炎症和抑郁发生率
- 批准号:
8712413 - 财政年份:2012
- 资助金额:
$ 53.5万 - 项目类别:
Sleep, Inflamation, and Depression Occurrence in Breast Cancer Survivors
乳腺癌幸存者的睡眠、炎症和抑郁发生率
- 批准号:
9128555 - 财政年份:2012
- 资助金额:
$ 53.5万 - 项目类别:
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