Brain Pathophysiology of Osteoarthritis Pain
骨关节炎疼痛的脑病理生理学
基本信息
- 批准号:10539290
- 负责人:
- 金额:$ 68.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-02-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AgeBehavioralBrainCharacteristicsChronicClinicalCognitionCognitiveDataDegenerative polyarthritisDependenceEmotionalEmotionsEsthesiaExcisionFailureFemaleFunctional Magnetic Resonance ImagingFunctional disorderFundingGoalsHealthcareHelping to End Addiction Long-termHippocampusIndividualJointsKneeKnee OsteoarthritisKnowledgeLinkMaintenanceMapsMeasuresModelingMoodsMotorNeocortexNeurologicNociceptionNociceptorsOperative Surgical ProceduresOutcomeOutcome AssessmentPainPain intensityPain managementParticipantPatient SchedulesPatientsPeripheralPersonalityPersonality AssessmentPersonsPharmaceutical PreparationsPopulationProcessPropertyPsychophysicsPsychosocial FactorQuestionnairesReplacement ArthroplastyRestRoleSensorySpinal CordStructureSubgroupTechnologyTestingTimeUnited States National Institutes of HealthValidationbrain circuitrycentral paincentral sensitizationchronic musculoskeletal painchronic painchronic pain reliefchronic painful conditioncohortcostdesignknee painknee replacement arthroplastylongitudinal designmalemultimodal neuroimagingneocorticalnew therapeutic targetnovel therapeuticsopioid epidemicopioid useosteoarthritis painpain patientpain reliefpatient subsetspharmacologicpredictive modelingpsychosocialresponsesexstudy characteristicssuccesssurgery outcomesurgical paintool
项目摘要
Abstract:
This is a revised proposal in response to PA-18-141 and the NIH HEAL initiative, designed to unravel
mechanisms that underlie chronic osteoarthritis (OA) knee pain. OA is the leading musculoskeletal chronic pain
condition worldwide, yet little is known about the mechanisms of chronic OA pain, reflected in the fact that current
pharmacologic approaches are minimally effective and new treatments have not been developed. In contrast,
joint replacement surgery is highly effective in most, but not all, patients with OA. For unknown reasons, around
20% (>140,000 cases in 2017 in the US alone) of OA knee replacement surgeries (TKR) fail to relieve pain. We
and others have shown that in people with chronic OA pain, the brain shows maladaptive reorganization of the
neocortex, diminished volumes of sub-cortical limbic structures, distinct brain activity for OA pain, and global
disruption of functional information integration. Together these results imply altered personality, psychosocial
status, and abnormalities in abilities for cognition, emotion, sensation and motor function (CESM-abilities), which
to our knowledge remain essentially unexplored in OA. In addition, nociceptive processes (peripheral and central
sensitization, descending modulation) have been considered as possibly being important for chronicity of OA.
Hence, the primary goals of this proposal are (1) to characterize the neurologic mechanisms for chronic OA knee
pain, and (2) to define neurologic mechanisms that differentiate success and failure of TKR. We propose testable
hypotheses regarding mechanisms underlying chronic OA pain and those that control TKR outcomes. In Aim 1,
we will study a large group of OA pain patients prior to TKR, as well as OA pain patients not undergoing TKR
(positive control) and healthy individuals (negative control), to characterize brain circuitries (T1, DMRI, resting
state fMRI) and determine how these map to nociception, to pain and related psychosocial status, personality,
and CESM-abilities. Since ~80% of TKR are successful in the long term (12 months), we hypothesize that in
these cases, the dominant parameter controlling pain is the OA joint-related nociceptive processes; while in
cases where TKR fails in the long term, there is a stronger dependence on psychosocial attributes and
personality (based on limbic brain properties). The latter hypothesis will be tested both over the short term (3
months post-TKR in Aim 2A) and in the long term (12 months post-TKR in Aim 2B), by constructing models
from pre-TKR measures (collected in aim 1) to predict knee pain in the short and long term after TKR. In Aim
3, subgroups of patients with the greatest and least pain relief at 3 months post-TKR will be fully reassessed for
outcomes deemed relevant (in Aim 1), followed, and then reassessed again at 12 months post-TKR. Outcome
contrasts between groups, and within groups in time, will allow us to identify consequences of knee surgery.
These outlined studies expand on our current knowledge regarding mechanisms of chronic pain in general, and
more specifically for OA and for post-TKR pain, potentially unraveling novel therapeutic targets.
抽象的:
这是针对 PA-18-141 和 NIH HEAL 倡议的修订提案,旨在解决
慢性骨关节炎(OA)膝关节疼痛的机制。 OA 是主要的肌肉骨骼慢性疼痛
但对于慢性 OA 疼痛的机制却知之甚少,这反映在当前的事实中:
药物方法的效果甚微,并且尚未开发出新的治疗方法。相比之下,
关节置换手术对大多数(但不是全部)骨关节炎患者非常有效。不知什么原因,周围
20%(仅在美国 2017 年就有超过 140,000 例)骨关节炎膝关节置换手术 (TKR) 无法缓解疼痛。我们
等人表明,患有慢性骨关节炎疼痛的人,大脑表现出适应不良的重组
新皮质、皮质下边缘结构体积减少、OA 疼痛的独特大脑活动以及整体
功能性信息整合的破坏。这些结果共同意味着人格、心理社会的改变
认知、情感、感觉和运动功能(CESM-能力)的状态和异常,
据我们所知,OA 领域基本上尚未被探索。此外,伤害感受过程(外周和中枢)
敏化、下降调制)被认为可能对 OA 的慢性化很重要。
因此,该提案的主要目标是(1)描述慢性膝关节骨关节炎的神经机制
(2) 定义区分 TKR 成功和失败的神经机制。我们建议可测试
关于慢性 OA 疼痛的机制和控制 TKR 结果的假设。在目标 1 中,
我们将研究大量进行 TKR 之前的 OA 疼痛患者,以及未接受 TKR 的 OA 疼痛患者
(阳性对照)和健康个体(阴性对照),以表征大脑回路(T1、DMRI、静息状态)
状态 fMRI)并确定这些如何映射到伤害感受、疼痛和相关的心理社会状态、性格、
和CESM能力。由于约 80% 的 TKR 从长期(12 个月)来看是成功的,因此我们假设
在这些病例中,控制疼痛的主要参数是 OA 关节相关的伤害性过程;当在
在 TKR 长期失败的情况下,对心理社会属性的依赖性更强,并且
个性(基于边缘脑特性)。后一个假设将在短期内得到检验(3
目标 2A 中的 TKR 后几个月)和长期(目标 2B 中的 TKR 后 12 个月),通过构建模型
根据 TKR 前的测量(在目标 1 中收集)来预测 TKR 后短期和长期的膝关节疼痛。瞄准
3、TKR 后 3 个月时疼痛缓解程度最大和最小的患者亚组将被全面重新评估
被认为相关的结果(在目标 1 中),随后进行跟踪,然后在 TKR 后 12 个月再次重新评估。结果
组之间以及组内时间的对比将使我们能够确定膝关节手术的后果。
这些概述的研究扩展了我们目前关于慢性疼痛机制的知识,并且
更具体地说,针对 OA 和 TKR 后疼痛,可能会揭示新的治疗靶点。
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Reorganization of functional brain network architecture in chronic osteoarthritis pain.
慢性骨关节炎疼痛中功能性脑网络结构的重组。
- DOI:
- 发表时间:2021
- 期刊:
- 影响因子:4.8
- 作者:Barroso, Joana;Wakaizumi, Kenta;Reis, Ana Mafalda;Baliki, Marwan;Schnitzer, Thomas J;Galhardo, Vasco;Apkarian, Apkar Vania
- 通讯作者:Apkarian, Apkar Vania
Deconstructing biomarkers for chronic pain: context- and hypothesis-dependent biomarker types in relation to chronic pain.
解构慢性疼痛的生物标志物:与慢性疼痛相关的背景和假设依赖的生物标志物类型。
- DOI:
- 发表时间:2019
- 期刊:
- 影响因子:7.4
- 作者:Reckziegel, Diane;Vachon;Petre, Bogdan;Schnitzer, Thomas J;Baliki, Marwan N;Apkarian, A Vania
- 通讯作者:Apkarian, A Vania
Prognostics for pain in osteoarthritis: Do clinical measures predict pain after total joint replacement?
骨关节炎疼痛的预后:临床测量是否可以预测全关节置换术后的疼痛?
- DOI:
- 发表时间:2020
- 期刊:
- 影响因子:3.7
- 作者:Barroso, Joana;Wakaizumi, Kenta;Reckziegel, Diane;Pinto;Schnitzer, Thomas;Galhardo, Vasco;Apkarian, A Vania
- 通讯作者:Apkarian, A Vania
Brain gray matter abnormalities in osteoarthritis pain: a cross-sectional evaluation.
骨关节炎疼痛中的脑灰质异常:横断面评估。
- DOI:
- 发表时间:2020
- 期刊:
- 影响因子:7.4
- 作者:Barroso, Joana;Vigotsky, Andrew D;Branco, Paulo;Reis, Ana Mafalda;Schnitzer, Thomas J;Galhardo, Vasco;Apkarian, A Vania
- 通讯作者:Apkarian, A Vania
Mechanical hyperalgesia and neuropathic pain qualities impart risk for chronic postoperative pain after total knee replacement.
机械性痛觉过敏和神经性疼痛会增加全膝关节置换术后慢性术后疼痛的风险。
- DOI:
- 发表时间:2024-01-17
- 期刊:
- 影响因子:0
- 作者:Vigotsky, Andrew D;Cong, Olivia;Pinto, Camila B;Barroso, Joana;Perez, Jennifer;Petersen, Kristian Kjaer;Arendt;Hardt, Kevin;Manning, David;Apkarian, A Vania;Branco, Paulo
- 通讯作者:Branco, Paulo
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Apkar Vania Apkarian其他文献
Apkar Vania Apkarian的其他文献
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{{ truncateString('Apkar Vania Apkarian', 18)}}的其他基金
Brain-based and clinical phenotyping of pain pharmacotherapy in knee OA
膝关节 OA 疼痛药物治疗的脑基和临床表型
- 批准号:
10735060 - 财政年份:2023
- 资助金额:
$ 68.98万 - 项目类别:
Brain reorganization in chronic back pain and opioid exposure
慢性背痛和阿片类药物暴露的大脑重组
- 批准号:
10440294 - 财政年份:2018
- 资助金额:
$ 68.98万 - 项目类别:
Brain reorganization in chronic back pain and opioid exposure
慢性背痛和阿片类药物暴露的大脑重组
- 批准号:
10198885 - 财政年份:2018
- 资助金额:
$ 68.98万 - 项目类别:
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