CRCN: Dissecting Neural Circuits for Acute Pain

CRCN：剖析急性疼痛的神经回路

• 批准号: 9313960
• 负责人: Zhe Sage Chen
• 金额: $ 37.08万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9313960
• 关键词: Absence of pain sensation; Acute Pain; Adverse effects; Affective; Analgesics; Anterior; Area; Base of the Brain; Behavior; Biological Assay; Brain; Brain region; Cells; Clinical Treatment; Code; Comb animal structure; Data; Data Analyses; Deep Brain Stimulation; Detection; Electrophysiology (science); Engineering; Goals; Health; Human; Individual; Instruction; Life; Methods; Modeling; Molecular; Motivation; Neuraxis; Neurons; Outcome; Pain; Pain management; Patients; Pattern; Peripheral; Pharmacology; Physiology; Play; Population; Prefrontal Cortex; Rattus; Reporting; Research; Rodent Model; Role; Sensory; Signal Transduction; Somatosensory Cortex; Spinal; Statistical Methods; Stimulus; Synapses; System; Techniques; Testing; Therapeutic; Time; Use Effectiveness; Work; arm; base; brain machine interface; central pain; cingulate cortex; clinical Diagnosis; computational neuroscience; design; experience; human imaging; imaging study; neural circuit; neuroimaging; neuromechanism; neuroregulation; next generation; novel; optogenetics; pain behavior; pain symptom; prototype; relating to nervous system; temporal measurement; tool; translational impact

Pain is a multidimensional experience that includes sensory and affective components. Human imaging studies have identified patterns of activities within key cortical areas that can encode different pain experiences, but it remains unclear how pain can also be encoded reliably at the level of individual neurons or populations of neurons. The primary somatosensory cortex (S1) has been thought to be important in the sensory-discriminative aspect of the pain, yet the anterior cingulate cortex (ACC) is known to play a crucial role in the affective-motivational experience of pain. However, imaging studies cannot provide causal relationship between circuits and behavior and are further limited by poor temporal resolution. Therefore, a complete understanding of neural codes for acute pain in physiology remains missing. Neuromodulation is a potential option for pain treatment; but current techniques such as deep brain stimulation (DBS) lack optimal targets and require constant stimulation with undesired side effects. We will use a rat model to uncover pain mechanisms of key central neural circuits and develop a demand-based brain-machine interface (BMI) that integrates timely detection of the pain signal and precise temporal analgesic control. In Aim 1, we will identify cortical circuitry for encoding acute pain. We will collect simultaneous S1 and ACC ensemble recordings from freely behaving rats and characterize their firing patterns at both single cell and population levels. In Aim 2, we will determine how the central pain circuitry is altered by central vs. peripheral analgesic strategy using optogenetic and pharmacological approaches. In Aim 3, we will develop reliable computational strategies to decode acute pain based on neural ensemble recordings from the central pain circuits involving S1 and ACC. In Aim 4, we will develop a real-time closed-loop BMI system for modulating acute pain by combining a detection arm of neural decoding with a therapeutic arm of central neurostimulation. We will test its effectiveness using established pain behavior assays. Together, these results will enable us to dissect neural circuits and mechanisms for acute pain and provide a template for next-generation demand-based pain treatment. RELEVANCE (See Instructions): This project is aimed to dissect circuit mechanisms of acute pain and develop closed-loop BMI system for pain control. We will combine experimental, computational and engineering techniques to decode acute pain signals and apply them to develop real-time BMI system for pain modulation using neurostimulation. The proposed research will not only reveal important mechanisms of acute pain, but will also provide new insiahts on theraoeutic treatment of oain analaesia.

疼痛是一种多维体验，包括感官和情感成分。人类成像 研究已经确定了可以编码不同疼痛的关键皮质区域内活动模式 经验，但目前尚不清楚如何在单个神经元的水平上可靠地编码疼痛 或神经元种群。原发性体感皮质（S1）被认为在 疼痛的感觉歧义方面，但已知前扣带回皮质（ACC）起着至关重要的作用 在疼痛的情感动机体验中的作用。但是，成像研究无法提供因果关系 电路与行为之间的关系，并受到时间分辨率差进一步限制。因此， 完全了解生理急性疼痛的神经法规仍然缺失。神经调节为a 疼痛治疗的潜在选择；但是当前的技术（例如深脑刺激（DB））缺乏最佳 目标并需要持续的刺激，并具有不希望的副作用。我们将使用大鼠模型发现疼痛 关键中央神经回路的机制，并开发出基于需求的脑机界面（BMI） 及时地集成了疼痛信号和精确的暂时镇痛控制的检测。在AIM 1中，我们将确定 用于编码急性疼痛的皮质回路。我们将同时收集S1和ACC合奏录音 从自由行为的大鼠中表征其在单细胞和人群水平上的发射模式。在 AIM 2，我们将确定中央疼痛电路如何通过中央与周围镇痛策略改变 使用光遗传学和药理方法。在AIM 3中，我们将开发可靠的计算 基于中央疼痛电路的神经合奏记录来解码急性疼痛的策略 S1和ACC。在AIM 4中，我们将开发一个实时闭环BMI系统，用于通过 将神经解码的检测臂与中央神经刺激的治疗臂结合在一起。我们将测试 使用既定的疼痛行为分析的有效性。这些结果在一起将使我们能够剖析 神经回路和急性疼痛的机制，并为下一代需求提供模板 疼痛治疗。 相关性（请参阅说明）： 该项目的目的是剖析急性疼痛的电路机制，并开发用于闭环BMI系统 疼痛控制。我们将结合实验，计算和工程技术来解码急性疼痛 信号并将其应用于使用神经刺激的实时BMI系统进行疼痛调节。这 拟议的研究不仅会揭示急性疼痛的重要机制，而且还将提供新的 Oain Analaesia的静脉治疗方法。