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: 7561591
• 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/7561591
• 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; 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; depression; 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（由申请人提供）：福格蒂国际研究合作奖的续签建立在中国北京的 P.I. Fie Luo 博士和 Drs. Fie Luo 之间的合作基础上。北卡罗来纳州神经科学研究所的 Jingyu Chang 和 D. Woodward。其目标是协调共同努力，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大脑结构的影响时间过程和作用机制。最初的研究重点是啮齿动物帕金森病模型的功能恢复。主要工作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，该仪器是在美国专门为这些研究而开发的。在我们的共同努力下，楼博士被任命为教授，中国科学院心理研究所也获得了新的实验室资源。我们小组现在的目标是大幅扩展 DBS 机制的研究主题，包括神经病理条件下中枢疼痛通路的调节。北卡罗莱纳州站点新录音能力的不断开发将与其他受支持的团体同时扩大北京的容量。当前研究的目标是阐明慢性疼痛条件下有效的深部脑刺激（DBS）的潜在机制。目的1是利用多区域的集合神经元记录来研究在局部炎症或脊神经结扎诱发疼痛后的时间过程中丘脑皮质通路中集合神经活动的动态变化。目的是检验周围炎症或神经病变会破坏这些通路中正常神经元处理的假设。目标 2 是研究慢性疼痛大鼠模型中丘脑皮质回路对行为有效的 DBS 的神经反应。目的是检验以下假设：高频刺激 VPL（丘脑腹后外侧核）和 PAG（导水管周围灰质）可恢复在慢性疼痛情况下未正确调节的丘脑皮质通路的正常处理。将采用清醒自由活动动物的多通道单单元电生理记录技术来揭示丘脑皮质区域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。这项研究将极大地增进我们对 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，即利用记录丘脑皮层神经活动的实时神经网络信息来改善和优化 DBS 对疼痛患者的效果。我们的合作将继续对与疼痛调节相关的中枢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系统疾病，影响着数百万患者。其中许多患者对常规医疗没有反应。因此，深部脑刺激为缓解慢性疼痛提供了一种有前途的替代方案。该研究项目将研究疼痛过程的神经机制以及深部脑刺激对动物模型慢性疼痛的影响。该研究将有助于我们在临床上更好地应用脑深部刺激来治疗顽固性疼痛。