Brain Pathophysiology of Osteoarthritis Pain

骨关节炎疼痛的脑病理生理学

• 批准号: 10539290
• 负责人: Apkar Vania Apkarian
• 金额: $ 68.98万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10539290
• 关键词: Age; Behavioral; Brain; Characteristics; Chronic; Clinical; Cognition; Cognitive; Data; Degenerative polyarthritis; Dependence; Emotional; Emotions; Esthesia; Excision; Failure; Female; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Healthcare; Helping to End Addiction Long-term; Hippocampus; Individual; Joints; Knee; Knee Osteoarthritis; Knowledge; Link; Maintenance; Maps; Measures; Modeling; Moods; Motor; Neocortex; Neurologic; Nociception; Nociceptors; Operative Surgical Procedures; Outcome; Outcome Assessment; Pain; Pain intensity; Pain management; Participant; Patient Schedules; Patients; Peripheral; Personality; Personality Assessment; Persons; Pharmaceutical Preparations; Population; Process; Property; Psychophysics; Psychosocial Factor; Questionnaires; Replacement Arthroplasty; Rest; Role; Sensory; Spinal Cord; Structure; Subgroup; Technology; Testing; Time; United States National Institutes of Health; Validation; brain circuitry; central pain; central sensitization; chronic musculoskeletal pain; chronic pain; chronic pain relief; chronic painful condition; cohort; cost; design; knee pain; knee replacement arthroplasty; longitudinal design; male; multimodal neuroimaging; neocortical; new therapeutic target; novel therapeutics; opioid epidemic; opioid use; osteoarthritis pain; pain patient; pain relief; patient subsets; pharmacologic; predictive modeling; psychosocial; response; sex; study characteristics; success; surgery outcome; surgical pain; tool

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： 这是对PA-18-141和NIH Heal倡议的响应的修订建议，旨在解开 慢性骨关节炎（OA）膝盖疼痛的机制。 OA是领先的肌肉骨骼慢性疼痛 全球疾病，但对慢性OA疼痛的机制知之甚少，这反映了 药理学方法是最小有效的，尚未开发新的治疗方法。相比之下， 关节置换手术在大多数（但不是全部）OA患者中非常有效。由于未知原因，周围 OA膝盖置换手术（TKR）20％（仅在2017年就在2017年> 140,000例）无法缓解疼痛。我们 其他人则表明，在患有慢性OA疼痛的人中，大脑显示出适应不良的重组 新皮层，下皮层边缘结构的体积减少，OA疼痛的不同大脑活动和全局 功能信息集成的破坏。这些结果在一起意味着个性改变，社会心理 认知，情感，感觉和运动功能（CESM能力）的能力的状态和异常，这些能力（能力） 据我们所知，在OA中基本上没有探索。另外，伤害性过程（外围和中央 敏化，下降调制）被认为对OA的慢性性可能很重要。 因此，该提案的主要目标是（1）表征慢性OA膝盖的神经系统机制 疼痛和（2）定义区分TKR成功和失败的神经系统机制。我们建议可测试 关于慢性OA疼痛和控制TKR结果的机制的假设。在AIM 1中， 我们将在TKR之前研究大量的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），以表征脑电路（T1，DMRI，静止 状态fMRI），并确定这些如何映射到伤害感受，痛苦和相关的社会心理状况，个性， 和CESM功能。由于大约80％的TKR在长期（12个月）中取得了成功，因此我们假设 这些情况下，控制疼痛的主要参数是与联合关节相关的伤害性过程。同时在 从长远来看，TKR失败了，对社会心理属性和 个性（基于边缘大脑特性）。后一种假设将在短期内进行测试（3 在AIM 2A中进行TKR之后的几个月）和长期（AIM 2B的TKR之后12个月），通过构建模型 根据TKR前的测量（在AIM 1中收集），以预测TKR后的短期和长期膝盖疼痛。目标 3，TKR后3个月的最大疼痛缓解疼痛的患者的亚组将被充分重新评估 结果被认为是相关的（在AIM 1中），然后在TKR后12个月再次重新评估。结果 组之间以及及时的组之间的对比，将使我们能够确定膝盖手术的后果。 这些概述的研究扩展了我们当前关于一般慢性疼痛机制的知识，以及 更具体地针对OA和TKR后疼痛，可能会揭示新的新型治疗靶标。

项目成果

Neural and Genetic Bases for Human Ability Traits.

• DOI: 10.3389/fnhum.2020.609170
• 发表时间: 2020
• 期刊: Frontiers in human neuroscience
• 影响因子: 2.9
• 作者: Pinto CB;Bielefeld J;Jabakhanji R;Reckziegel D;Griffith JW;Apkarian AV
• 通讯作者: Apkarian AV

Reorganization of functional brain network architecture in chronic osteoarthritis pain.

• DOI: 10.1002/hbm.25287
• 发表时间: 2021-03
• 期刊: Human brain mapping
• 影响因子: 4.8
• 作者: Barroso J;Wakaizumi K;Reis AM;Baliki M;Schnitzer TJ;Galhardo V;Apkarian AV
• 通讯作者: Apkarian AV

Brain gray matter abnormalities in osteoarthritis pain: a cross-sectional evaluation.

• DOI: 10.1097/j.pain.0000000000001904
• 发表时间: 2020-09-01
• 期刊: Pain
• 影响因子: 7.4
• 作者: Barroso J;Vigotsky AD;Branco P;Reis AM;Schnitzer TJ;Galhardo V;Apkarian AV
• 通讯作者: Apkarian AV

Brain mechanisms of chronic pain: critical role of translational approach.

• DOI: 10.1016/j.trsl.2021.06.004
• 发表时间: 2021-12
• 期刊: Translational research : the journal of laboratory and clinical medicine
• 作者: Barroso J;Branco P;Apkarian AV
• 通讯作者: Apkarian AV

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: 10.1101/2024.01.16.24301372
• 发表时间: 2024
• 期刊: medRxiv : the preprint server for health sciences
• 作者: Vigotsky,AndrewD;Cong,Olivia;Pinto,CamilaB;Barroso,Joana;Perez,Jennifer;Petersen,KristianKjaer;Arendt-Nielsen,Lars;Hardt,Kevin;Manning,David;Apkarian,AVania;Branco,Paulo
• 通讯作者: Branco,Paulo