CRCN: Dissecting Neural Circuits for Acute Pain

CRCN：剖析急性疼痛的神经回路

• 批准号: 9242180
• 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/9242180
• 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; Image; Individual; Instruction; Life; Methods; Modeling; Molecular; Neuraxis; Neurons; Outcome; Pain; Pain management; Patients; Pattern; Peripheral; 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; neural circuit; neuroimaging; neuromechanism; neuroregulation; next generation; novel; optogenetics; pain behavior; pain symptom; prototype; relating to nervous system; temporal measurement; tool

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，包括感觉和情感成分。人体成像 研究已经确定了关键皮质区域内可编码不同疼痛的活动模式 体验，但尚不清楚疼痛如何也能在单个神经元水平上可靠地编码 或者是神经元群体。初级躯体感觉皮层(S1)一直被认为在 疼痛的感觉辨别方面，但已知前扣带皮质(ACC)在 在痛苦的情感激励体验中扮演的角色。然而，影像研究不能提供因果关系。 电路和行为之间的关系，并进一步受到较差的时间分辨率的限制。因此，a 对急性生理学疼痛的神经编码的完整理解仍然缺乏。神经调节是一种 治疗疼痛的潜在选择；但目前的技术，如脑深部刺激(DBS)，缺乏最佳方案 而且需要持续的刺激，有不良的副作用。我们将使用一个老鼠模型来揭示疼痛 关键中枢神经回路的机制，并开发基于需求的脑机接口(BMI)， 集成了疼痛信号的及时检测和精确的暂时止痛控制。在目标1中，我们将确定 用于编码急性疼痛的大脑皮层回路。我们将收集同时进行的S1和ACC合奏录音 从自由行为的大鼠，并在单细胞和种群水平表征它们的放电模式。在……里面 目的2，我们将确定中枢与外周止痛策略是如何改变中枢痛路的。 使用光遗传学和药理学方法。在目标3中，我们将开发可靠的计算 基于中枢疼痛环路的神经集成记录解码急性疼痛的策略 S1和Acc.在目标4中，我们将开发一个实时闭环BMI系统，用于通过以下方式调节急性疼痛 将神经解码的检测臂与中枢神经刺激的治疗臂相结合。我们将测试 使用已建立的疼痛行为分析来评估其有效性。总而言之，这些结果将使我们能够剖析 急性疼痛的神经电路和机制，并为下一代基于需求的 疼痛治疗。 相关性(请参阅说明)： 本项目旨在剖析急性疼痛的电路机制，并开发用于急性疼痛的闭环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 并将其应用于开发利用神经刺激进行疼痛调制的实时BMI系统。这个 拟议中的研究不仅将揭示急性疼痛的重要机制，还将提供新的 过敏性贫血的治疗探讨