Effect of deep brain stimulation on thalamocortical pain processing

描述（由申请人提供）：福格蒂国际研究合作奖的更新建立在中国北京的私家侦探罗菲博士和福格蒂博士之间的合作基础上。北卡罗来纳神经科学研究所的张靖宇和伍德沃德博士说。目的是协调共同努力，了解脑深部刺激对帕金森病、癫痫控制和相关脑功能的不同脑结构的作用的时间过程和作用机制。最初的研究集中在帕金森病啮齿动物模型的功能恢复。主要工作包括在罗博士的实验室共享和建立用于联合刺激和记录的先进仪器，这些仪器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，娄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。我们的小组现在定位于实质性地扩展DBS机制的研究主题，包括神经性疾病下中枢疼痛通路的调节。北卡罗莱纳基地不断发展新的记录能力，将扩大北京基地的记录能力，与其他受支持的组织同步进行。本研究的目的是阐明慢性疼痛条件下有效深部脑刺激（DBS）的机制。目的1是利用多区域的集合神经元记录，研究局部炎症或脊神经结扎引起疼痛后，丘脑皮质通路中集合神经活动的动态变化。目的是验证周围炎症或神经病变会破坏这些通路中正常的神经元处理的假设。目的2研究慢性疼痛模型大鼠丘脑皮质回路对行为有效DBS的神经反应。目的是验证高频率刺激VPL（丘脑腹侧后外侧核）和PAG（导管周围灰质）恢复在慢性疼痛条件下不正确调节的丘脑皮质通路的正常处理的假设。采用清醒自由运动动物的多通道单单元电生理记录技术，揭示丘脑皮质区神经元的动态活动模式。Freund's完全佐剂诱导的炎症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，本研究的成功将为未来的目标奠定基础，即利用从记录丘脑皮质整体神经活动中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脑区域的多种功能进行基础研究。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。这些患者中有许多对传统医学治疗没有反应。因此，深部脑刺激为减轻慢性疼痛提供了一种有希望的替代方案。本课题将在动物模型上研究疼痛过程的神经机制和脑深部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应用于临床治疗顽固性疼痛。

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.