Pain Mechanisms for New Onset and Chronic HIV Distal Neuropathic Pain

新发和慢性 HIV 远端神经病理性疼痛的疼痛机制

• 批准号: 8541531
• 负责人: John R Keltner
• 金额: $ 15.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8541531
• 关键词: AIDS neuropathy; Address; Affect; American; Anesthesia procedures; Area; Atrophic; Back Pain; Basic Science; Biological Markers; Biopsy; Brain; Brain imaging; California; Chronic; Clinical; Clinical Research; Clinical assessments; Coupled; Critiques; Cross-Sectional Studies; Development; Diabetes Mellitus; Diffusion; Distal; Doctor of Philosophy; Enrollment; Environment; Epidemic; Fellowship; Functional Imaging; Functional disorder; Goals; HIV; Heart Diseases; Individual; Insula of Reil; K-Series Research Career Programs; Magnetic Resonance; Malignant Neoplasms; Measures; Mentors; Methods; Mood Disorders; Morbidity - disease rate; Nerve Fibers; Neural Conduction; Neuraxis; Neuropathy; Outcome; Pain; Pain Disorder; Pain Research; Pain management; Participant; Patients; Peripheral; Peripheral Nervous System Diseases; Physics; Process; Psychiatry; Quality of life; Recruitment Activity; Relative (related person); Research; Research Infrastructure; Research Methodology; Research Training; Residencies; Resistance; Rest; Risk; Role; Sampling; Sensory; Skin; Syndrome; Task Performances; Testing; Time; Training; Translational Research; Unemployment; Universities; Update; base; brain volume; career; central pain; cerebral atrophy; chronic neuropathic pain; chronic pain; daily functioning; design; gray matter; interest; medical schools; meetings; multidisciplinary; neurobehavioral; neuroimaging; neuropsychiatry; painful neuropathy; programs; public health relevance; research study; tool; white matter

DESCRIPTION (provided by applicant): CLINICAL PROBLEM: More Americans are affected by chronic pain than by heart disease, diabetes, and cancer combined. One of these pain syndromes is chronic HIV distal neuropathic pain (DNP), which has been termed an "emerging epidemic", and affects approximately 20% of all HIV patients. HIV DNP is treatment- resistant and is associated with impaired daily function, unemployment, and worse life quality. Most HIV DNP research to date has focused on the peripheral mechanisms, which has overlooked the role of brain mechanisms for HIV DNP. A better understanding of brain mechanisms for HIV DNP may be useful to identify individuals at risk for HIV DNP. Brain imaging is a tool to help understand central nervous system mechanisms and to identify candidate biomarkers, but despite its potential usefulness has never been used to investigate HIV DNP. CANDIDATE: My unique background should enable me to capitalize on the training and research proposed in this application. I obtained a Ph.D. in physics and was trained in brain neuroimaging. Afterwards I attended medical school where I developed an interest in chronic pain as well as the relationship between pain and mood disorders. Focusing on pain, I completed an anesthesia residency and a clinical fellowship in pain management, then conducted basic science functional neuroimaging pain research. As my interest in mood disorders and chronic pain deepened, I entered a clinical psychiatry residency program. In my last year of residency I focused on HIV-related pain and I have spent the past year as a part-time research fellow in NeuroAIDS investigating brain mechanisms for HIV distal neuropathic pain. TRAINING: Although I have a strong background in the basic sciences of functional neuroimaging and have completed clinical residencies, I have not been trained in the principles of clinical research nor in clinical research methods essential to my career such as methods for investigating pathophysiology of peripheral neuropathy, HIV neuromedical assessment and HIV neuropsychiatric assessment. The training proposed in this K-23 application is designed to address these shortcomings. Thereafter my long-term plans are to pursue a multi-disciplinary academic psychiatry translational research career striving to bridge basic science pain neuroimaging research with clinical pain psychiatry research. ENVIRONMENT: The University of California San Diego (UCSD) offers a unique training and research environment to investigate brain mechanisms of HIV distal neuropathic pain. This includes 1) The UCSD HIV Neurobehavioral Research Center (HNRC) facility infrastructure; 2) the HNRC multidisciplinary team of neuromedical, neuropsychiatric, and neuroimaging clinical research mentors; 3) The UCSD Keck Center for Functional Imaging facility; 4) consultants with an outstanding track record of research in chronic pain and in neuroimaging; and 5) access to a large sample of HIV patients in San Diego at the HIV Neurobehavioral Research Program which have been previously identified to have two or more signs of neuropathy with and without HIV distal neuropathic pain. RESEARCH PLAN: The translational research objective of this application is to use multi-modal magnetic resonance (MR) neuroimaging and clinical research characterization of HIV peripheral neuropathy, in concert with standardized pain, neuropsychiatric, and neuromedical assessment, to better understand central and peripheral mechanisms of HIV DNP for 3 clinical research groups which all have 2 or more signs of peripheral neuropathy but differ in presence and duration of DNP: Group 1 - no DNP, Group 2 - DNP with pain of 1 to 3 months duration on a daily or almost daily basis (at least 5 days/week), and Group 3 - DNP with daily or almost daily pain > 6 months. Two specific aims are 1) To determine if resting state functional imaging connectivity between brain processing areas, such as the insula cortex, and resting state default mode networks will be increased for individuals with pain (Groups 2 and 3) compared to those without pain (Group 1), and 2) To determine if regional brain volumes for brain pain processing areas such as the insula will be smaller for individuals with chronic pain (Group 3) compared to those without chronic pain (Groups 1 and 2). It is hypothesized that resting state functional insula connectivity with default mode networks will be higher for those with pain (Groups 2 and 3) compared to those without pain (Group 1), and that regional insula brain volumes will be smaller in chronic pain patients (Group 3) compared to the other two groups. Over a 4-year period research participants in these groups will be recruited from individuals enrolled in clinica research studies ongoing at the UCSD HIV Neurobehavioral Research Program (HNRP). Each group will be characterized by multi-modal neuroimaging (resting state functional, gray matter structural, and white matter diffusion tensor) and clinical assessment of HIV peripheral neuropathy (skin biopsy, quantitative sensory testing, and nerve conduction testing), in concert with standardized pain, neuropsychiatric, and neuromedical assessment.

描述（由申请人提供）：临床问题：比心脏病，糖尿病和癌症加在一起的美国人受慢性疼痛的影响更多。这些疼痛综合征之一是慢性HIV远端神经性疼痛（DNP），该疼痛被称为“新兴流行病”，影响了所有HIV患者的20％。艾滋病毒DNP具有抗药性，与日常功能受损，失业和较差的生活质量有关。迄今为止，大多数HIV DNP研究都集中在外围机制上，该机制忽略了HIV DNP的大脑机制的作用。对HIV DNP的大脑机制的更好理解对于鉴定有艾滋病毒DNP风险的个体可能很有用。脑成像是一种工具，可以帮助了解中枢神经系统机制并识别候选生物标志物，但是尽管其潜在的有用性从未用于研究HIV DNP。候选人：我独特的背景应该使我能够利用本应用程序中提出的培训和研究。我获得了博士学位。在物理学中，接受了大脑神经影像的培训。之后，我上了医学院，在那里我对慢性疼痛以及疼痛和情绪障碍之间的关系产生了兴趣。重点关注疼痛，我完成了麻醉居留和疼痛管理方面的临床研究金，然后进行了基础科学功能性神经影像学研究。随着我对情绪障碍和慢性疼痛的兴趣加深，我进入了临床精神病学居住计划。在居住的最后一年，我专注于与HIV相关的疼痛，在过去的一年中，我一直担任神经助理研究研究员，研究了HIV HIV远端神经性疼痛的脑机制。培训：尽管我在功能性神经影像学的基本科学方面具有良好的背景，并且已经完成了临床居住居住，但我尚未接受过临床研究原理的培训，也没有接受过我职业所必需的临床研究方法，例如研究外周神经病变，HIV神经医学评估和HIV神经神经医学评估和HIV神经心理评估的方法。该K-23应用程序中提出的培训旨在解决这些缺点。此后，我的长期计划是通过临床疼痛精神病学研究来追求多学科的学术精神病学转化研究职业，努力弥合基础科学疼痛神经影像学研究。环境：加州大学圣地亚哥分校（UCSD）提供了独特的培训和研究环境，以研究HIV远端神经性疼痛的大脑机制。其中包括1）UCSD HIV神经行为研究中心（HNRC）设施基础设施； 2）神经医学，神经精神病学和神经成像临床研究导师的HNRC多学科团队； 3）UCSD凯克功能成像设施中心； 4）具有出色的慢性疼痛研究和神经影像学研究记录的顾问； 5）在HIV神经行为研究计划中，可以访问圣地亚哥的大量艾滋病毒患者样本，该研究以前已被确定为具有和没有HIV远端神经性疼痛的两个或更多迹象的神经性迹象。 研究计划：本应用的转化研究目标是使用多模式磁共振（MR）神经影像学和临床研究表征对HIV周围神经病的表征，与标准化疼痛，神经精神上的神经医学和神经医学评估一致，以更好地了解HIV的NIV和外围研究组的NIV dnp eip dnp或更多符号的3个临床迹象，这些临床研究范围有3个临床研究的范围或更多符号，这些临床研究的范围是2或更多。在DNP的存在和持续时间：第1组-NO DNP，第2组-DNP，每天或几乎每天（至少5天/周）和第3组-DNP，每天或每天疼痛> 6个月，疼痛为1至3个月。两个具体的目的是1）确定脑处理区域之间的静止状态功能成像连通性（例如裂纹皮层）和静止状态默认模式网络是否会增加疼痛的个体（第2组和第3组）与没有疼痛的人（第2组和第3组）（第1组和2组）（第1组）和2），以确定诸如较小的iNsula shime pain（组合较小的人）（组合较小的人）（组合3）是否为较小的脑部疼痛（小组）（组合3）。假设与没有疼痛的患者相比，患有疼痛的人（第2和3组）的静息状态功能性岛连接将更高（第2组和第3组），而与其他两组相比，慢性疼痛患者（第3组）的区域绝缘脑体积将较小。在四年内，这些小组的研究参与者将从参加UCSD HIV神经行为研究计划（HNRP）正在进行的临床研究的个人中招募。每个组的特征是多模式神经影像（静止状态功能，灰质结构和白质扩散张量）和HIV周围神经病变的临床评估（皮肤活检，定量感觉测试和神经传导测试），并与标准化的疼痛，神经精神上的疼痛，Neuropsychiatial and Neuropical Irtricicals和Neuropsicticals和Neuropsicticals和Neuropsytricals和Neuropsytric sessent。