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Effect of deep brain stimulation on thalamocortical pain processing

脑深部电刺激对丘脑皮质疼痛处理的影响

基本信息

批准号：
8037717
负责人：
Fei Luo
金额：
$ 3.32万
依托单位：
INSTITUTE OF PSYCHOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2012-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8037717
关键词：
Academy Acupuncture procedure Affect Affective Aftercare Analgesics Animal Model Animals Anterior Applications Grants Appointment Area Award Basal Ganglia Behavioral Paradigm Biological Neural Networks Brain Brain region China Chinese People Chronic Clinic Clinical Clinical Research Clinical Trials Code Collaborations Computers and Advanced Instrumentation Contralateral Corpus striatum structure Country Deep Brain Stimulation Development Disease Dopamine Dopaminergic Cell Dorsal Electrodes Electronics Epilepsy Esthesia Exhibits Frequencies Freund&apos s Adjuvant Future Goals Grant Gray unit of radiation dose Hair Health Heating Hyperalgesia Implant Implanted Electrodes Inflammation Institutes International Intractable Pain Investigation Joints Knowledge Laboratories Lateral Lateral posterior nucleus of thalamus Lesion Ligation Light Limb structure Location Longitudinal Studies Mechanical Stimulation Mechanics Medial Mediating Medical Mental Depression Modeling Monitor Motor Movement National Institute of Neurological Disorders and Stroke Neurons Neuropathy Neurosciences Research Nociception Nociceptive Stimulus North Carolina Operative Surgical Procedures Pain Parents Parkinson Disease Parkinsonian Disorders Pathway interactions Patients Pattern Perception Peripheral Physiologic pulse Population Positioning Attribute Procedures Process Property Psychology Publications Rattus Regulation Reporting Research Research Institute Research Project Grants Resources Rodent Rodent Model Science Sensory Sensory Neglects Sensory Process Signal Transduction Site Small Business Innovation Research Grant Somatosensory Cortex Spinal nerve structure Stimulus Structure Subcutaneous Injections Subthalamic structure Support Groups Symptoms Syndrome System Techniques Testing Thalamic structure Therapeutic Effect Time Work awake central pain chronic pain cingulate cortex experience improved inflammatory pain insight instrumentation midbrain central gray substance motor control nervous system disorder neuromechanism neurophysiology novel strategies painful neuropathy parent grant professor relating to nervous system research study response restoration simulation success

项目摘要

DESCRIPTION (provided by applicant): This renewal of a Fogarty International Research Collaboration Award builds on collaboration between the P.I., Dr. Fie Luo, in Beijing China and Drs. Jingyu Chang and D. Woodward at the Neuroscience Research Institute of North Carolina. The goal was to coordinate a common effort to understand the time course of effect and mechanisms of action of deep brain stimulation on different brain structures for Parkinson's disease, epilepsy control, and related brain functions. Initial studies focused on restoration of function in models of Parkinson's disease in rodent. A major effort included sharing and establishing advanced instrumentation for combined stimulation and recording at Dr. Luo's laboratory that was developed at the USA site specifically for these studies. Success of our joint effort led to the appointment of Dr. Lou to Professor along with new laboratory resources at the Institute of Psychology Chinese Academy of Science. Our group is now positioned to expand substantially the research theme of DBS mechanism to include regulation of central pain pathways under neuropathic conditions. Continual development of new recording capabilities at the North Carolina site will expand the capacities at Beijing in parallel with other supported groups. The goal of the current study is to elucidate mechanisms underlying effective deep brain stimulation (DBS) under chronic pain conditions. Aim 1 is to employ ensemble neuron recording in multiple regions to investigate the dynamic changes of ensemble neural activity in the thalamocortical pathways during the time course following the induction of pain by local inflammation or by ligation of spinal nerve. The goal is to test the hypothesis that peripheral inflammation or neuropathy will disrupt normal neuronal processing in these pathways. Aim 2 is to study the neural responses of thalamocortical circuit to the behaviorally effective DBS in the rat models of chronic pain. The goal is to test the hypothesis that high frequency stimulation of VPL (ventral posterior lateral nucleus of thalamus) and PAG (periaqueductal gray) restored normal processing in the thalamocortical pathways that are not regulated correctly in the chronic pain condition. Multiple channel single-unit electrophysiological recording techniques in awake freely- moving animals will be employed to reveal the dynamic activity pattern of neurons in thalamocortical areas. Inflammatory pain induced by Freund's complete adjuvant, and spinal nerve ligation induced neuropathic pain models, will be used to mimic two major types of clinical chronic pain syndromes. This study will substantially advance our knowledge about the mechanisms underlying analgesic effect of DBS. Furthermore, success of this study will lay the groundwork for a future goal of using real-time neural network information obtained from recording ensemble thalamocortical neural activity to improve and optimize the effects of DBS in pain patients. Our collaboration will continue a basic investigation of multiple functions of the central brain regions related to pain regulation. PUBLIC HEALTH RELEVANCE: Pain is a common neurological disorder affecting millions of patients. Many of these patients are not responsive to conventional medical treatment. Deep brain stimulation thus provides a promising alternative for alleviate chronic pain. This research project will study the neural mechanisms underlying pain process and the effect of deep brain stimulation on chronic pain in animal models. The study will help us to better apply deep brain stimulation in the clinic to treat intractable pain.

描述（由申请人提供）：福格蒂国际研究合作奖的更新建立在P.I.，罗飞博士，中国北京，张静宇博士和D。伍德沃德在北卡罗来纳州的神经科学研究所。目的是协调共同努力，以了解深部脑刺激对帕金森病、癫痫控制和相关脑功能的不同脑结构的作用时间过程和作用机制。最初的研究集中在啮齿动物帕金森病模型中的功能恢复。一项重大努力包括在罗博士的实验室共享和建立用于组合刺激和记录的先进仪器，该仪器是在美国工厂专门为这些研究开发的。我们的共同努力的成功导致楼博士被任命为教授沿着新的实验室资源在中国科学院心理研究所。我们的小组现在定位于大幅扩展DBS机制的研究主题，以包括神经病理条件下中枢疼痛通路的调节。在北卡罗来纳州不断开发新的录音能力，将扩大在北京的能力，与其他支持团体平行。本研究的目的是阐明慢性疼痛条件下有效的脑深部电刺激（DBS）的机制。目的1：采用多区域神经元整体记录技术，研究局部炎症或脊神经结扎引起疼痛后丘脑皮质通路神经元整体活动的动态变化。目的是检验外周炎症或神经病变会破坏这些通路中正常神经元加工的假设。目的二是研究行为有效DBS对慢性痛模型大鼠丘脑皮层回路的神经反应。我们的目标是测试的假设，即高频刺激VPL（腹后外侧核丘脑）和PAG（导水管周围灰质）恢复正常的处理在丘脑皮质通路，在慢性疼痛的条件下，没有得到正确的调节。在清醒自由活动的动物中，将采用多通道单单位电生理记录技术来揭示丘脑皮质区神经元的动态活动模式。由弗氏完全佐剂诱导的炎性疼痛和脊神经结扎诱导的神经性疼痛模型将用于模拟两种主要类型的临床慢性疼痛综合征。这项研究将大大提高我们对DBS镇痛作用机制的认识。此外，这项研究的成功将为未来的目标奠定基础，即利用记录丘脑皮质神经活动的实时神经网络信息来改善和优化DBS在疼痛患者中的效果。我们的合作将继续对与疼痛调节相关的中枢脑区的多种功能进行基础研究。公共卫生相关性：疼痛是一种常见的神经系统疾病，影响数百万患者。这些患者中的许多人对常规药物治疗没有反应。因此，脑深部电刺激为缓解慢性疼痛提供了一种有前途的替代方案。本研究将在动物模型中研究疼痛过程的神经机制以及脑深部电刺激对慢性疼痛的影响。该研究将有助于我们更好地将脑深部电刺激术应用于临床治疗顽固性疼痛。