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（由申请人提供）：Fogarty International Research合作奖的这一续签基于P.I.，Fie Luo博士在北京中国和Drs之间的合作。北卡罗来纳州神经科学研究所的Jingyu Chang和D. Woodward。目的是协调一项共同的努力，以了解深度脑刺激对帕金森氏病，癫痫控制和相关大脑功能的大脑刺激对不同大脑结构的作用机制。最初的研究集中在啮齿动物中帕金森氏病模型中的功能恢复。一项重大努力包括共享和建立先进的仪器，以在Luo博士的实验室进行联合刺激和记录，该仪器是在美国专门针对这些研究的美国开发的。我们共同努力的成功导致了卢博士在中国科学学院的新实验室资源以及新的实验室资源。现在，我们的小组可以大大扩展DBS机制的研究主题，包括在神经性疾病条件下调节中枢疼痛途径。北卡罗来纳州现场的新录音能力的持续发展将与其他支持团体并行扩大北京的能力。当前研究的目的是阐明在慢性疼痛条件下有效的深脑刺激（DBS）的机制。目的1是在多个区域采用集合神经元记录来研究在局部炎症诱导疼痛或通过脊柱神经结扎后的时间过程中丘脑皮质途径中集合神经活动的动态变化。目的是检验以下假设：周围炎症或神经病会破坏这些途径中的正常神经元处理。目的2是研究丘脑皮质回路对慢性疼痛大鼠模型中行为有效DBS的神经反应。目的是检验以下假设：在慢性疼痛条件下未正确调控的丘脑皮质途径中，VPL的高频刺激VPL（丘脑的腹侧后侧核）和PAG（PeriaqueDuctal Gray）恢复了正常处理。多道通道单单元电生理记录技术将采用自由移动的动物来揭示丘脑皮质区域中神经元的动态活性模式。 Freund的完整佐剂和脊神经结扎诱导的神经性疼痛模型引起的炎症性疼痛将用于模仿两种主要类型的临床慢性疼痛综合症。这项研究将大大提高我们对DBS镇痛作用的机制的了解。此外，这项研究的成功将为未来的目标奠定基础，即使用记录集合丘脑皮质神经活动获得的实时神经网络信息，以改善和优化DBS对疼痛患者的影响。我们的合作将继续对与疼痛调节有关的中央大脑区域的多个功能进行基本研究。公共卫生相关性：疼痛是影响数百万患者的常见神经系统疾病。这些患者中的许多人对常规医疗没有反应。因此，大脑刺激为减轻慢性疼痛提供了有希望的替代方法。该研究项目将研究疼痛过程的神经机制以及深脑刺激对动物模型中慢性疼痛的影响。这项研究将帮助我们更好地在诊所中应用深脑刺激，以治疗顽固的疼痛。