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

• 批准号: 7771725
• 负责人: Fei Luo
• 金额: $ 3.35万
• 依托单位: INSTITUTE OF PSYCHOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2012-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7771725
• 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' s Adjuvant; Future; Goals; Grant; Gray unit of radiation dose; Hair; 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; public health relevance; relating to nervous system; research study; response; restoration; simulation; success

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(申请人提供)：本次Fogarty国际研究合作奖的续展建立在北京的私人助理罗飞博士与北卡罗来纳州神经科学研究所的张静瑜博士和D.Woodward博士之间的合作基础上。其目的是协调共同的努力，以了解深部脑刺激对帕金森氏病、癫痫控制和相关脑功能的不同脑结构的作用时间进程和作用机制。最初的研究集中在恢复啮齿动物帕金森氏病模型的功能上。一项主要的努力包括在罗博士的实验室共享和建立先进的组合刺激和记录仪器，该实验室是在美国专门为这些研究开发的。我们的共同努力取得了成功，楼博士被任命为中国科学院心理研究所的教授，并获得了新的实验室资源。我们小组现在准备大幅扩展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。北卡罗来纳州现场不断开发新的录音能力，将扩大北京的能力，同时扩大其他得到支持的团体的能力。本研究的目的是阐明慢性疼痛条件下有效的脑深部刺激(DBS)的机制。目的1研究局部炎症或脊神经结扎致痛后，丘脑皮质通路神经元整体活动的动态变化。我们的目标是测试外周炎症或神经病变将扰乱这些通路中正常神经元处理的假设。目的2研究慢性疼痛模型大鼠丘脑皮质环路对行为效应DBS的神经反应。目的是验证高频刺激丘脑腹后外侧核(VPL)和中脑导水管周围灰质(PAG)恢复丘脑皮质通路的正常加工的假说，这些通路在慢性疼痛条件下没有正确调节。利用清醒自由活动动物的多通道单单位电生理记录技术，揭示丘脑皮质区神经元的动态活动模式。弗氏完全佐剂诱导的炎性疼痛和脊神经结扎诱导的神经病理性疼痛模型将被用来模拟两种主要的临床慢性疼痛综合征。这项研究将极大地促进我们对DBS镇痛作用机制的了解。此外，这项研究的成功将为未来的目标奠定基础，该目标是使用从记录整体丘脑皮质神经活动获得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央大脑区域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疾病，影响着数百万患者。这些患者中的许多人对常规治疗没有反应。因此，脑深部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上研究疼痛过程的神经机制以及脑深部刺激对慢性疼痛的影响。本研究有助于更好地将脑深部电刺激应用于临床治疗顽固性疼痛。