Neuroimaging to identify the neural correlates of anesthetic and analgesic action in humans

神经影像学可识别人类麻醉和镇痛作用的神经相关性

• 批准号: 10795475
• 负责人: Keith Michael Vogt
• 金额: $ 5.41万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10795475
• 关键词: Absence of pain sensation; Acute Pain; Address; Adult; Affect; Amnesia; Analgesics; Anesthesia procedures; Anesthesiology; Anesthetics; Behavior; Behavioral; Biomedical Engineering; Brain; Clinical; Clinical Trials; Combination Medication; Complex; Conscious; Data; Data Analyses; Dexmedetomidine; Dose; Drug Interactions; Electroencephalography; Engineering; Ensure; Environment; Fentanyl; Foundations; Functional Magnetic Resonance Imaging; Goals; Human; Image; Individual; Investigation; Ketamine; Knowledge; Lidocaine; Magnetic Resonance Imaging; Measures; Memory; Midazolam; Modeling; Neurosciences; Neurosciences Research; Operative Surgical Procedures; Pain; Patients; Perioperative; Pharmaceutical Preparations; Pharmacology; Physicians; Placebo Control; Polypharmacy; Procedures; Productivity; Propofol; Psychology; Randomized; Research; Single-Blind Study; System; Time; Work; arm; clinical practice; cognitive function; cognitive task; conditioned fear; drug action; experience; heart rhythm; human subject; improved; innovation; multimodal data; neural; neural correlate; neuroimaging; pain processing; pain relief; prevent; programs; response; sevoflurane; trial comparing; volunteer

Project Summary This ESI MIRA program of research, within the field of anesthesiology and perioperative pain, is aimed at better understanding how anesthetic and analgesic agents block memory formation, prevent conditioned fear responses, and relieve pain during otherwise unbearable experiences. Current provision of clinical anesthesia is not universally effective in achieving these goals because of a critical knowledge gap in understanding the systems-level neuroscience of how these drugs act and interact. The PI is a physician-anesthesiologist and bioengineer who has established a unique and innovative interdisciplinary framework to address this important problem. A team of senior collaborators, with expertise in psychology, functional MRI analysis, MRI engineering, and anesthetic pharmacology has been assembled to take advantage of an extremely productive academic environment. The project will determine how anesthetics from the seven major mechanistic classes of clinically- used agents act and interact to affect cognitive functions, including where in the brain changes occur. Steady- state concentrations of anesthetics will be delivered in a high-field MRI environment, while subjects perform cognitive tasks with precisely timed acute pain stimulation; electroencephalography, electrodermal, and cardiac rhythm data will simultaneously be acquired. The inclusion of acute pain, use of high-field functional MRI, multimodal data and broad characterization of behavior all represent increased rigor compared to prior human anesthetic neuroscience work, and builds on the PI’s recent studying midazolam and ketamine. The first planned project will complete the mechanistic clinical trial comparing propofol, dexmedetomidine, and fentanyl, which has begun under the PI’s K23. This is a randomized placebo-controlled single-blind parallel arm neuroimaging study in healthy adult volunteers (NCT04062123). The second set of projects will examine lidocaine and sevoflurane, to complete the individual investigation of representative examples from each major mechanistic class of commonly-used anesthetics. The third set of proposed projects will address an important barrier to progress by employing combinations of anesthetics across two or more of the previously characterized mechanistic classes. This will mark a shift in the paradigm to more realistically model the polypharmacy that is ubiquitous in clinical anesthesia practice. Combinations of anesthetics will be constrained to those that would be feasible to implement together in clinical practice and selection will be based on a broad quantitative analysis of data obtained for each agent studied individually, with the goal of leveraging key synergistic behavioral and neural interactions across mechanistically-different anesthetics. The overall goal of this substantive program of systems-level neuroscience research is to identify the key neural signatures that are both necessary and sufficient for anesthetic-induced inhibition of memory formation, fear conditioning, and pain processing. This will lay the foundation needed to progress towards the long-term vision of improving clinical practice, through more informed dosing combinations or enhanced intraoperative measures, to ensure amnesia and analgesia for all patients under anesthesia.

项目摘要 在麻醉和周期性疼痛领域内的ESI MIRA研究计划旨在更好 了解麻醉和止痛药如何阻止记忆形成，防止有条件的恐惧 反应，并在其他难以忍受的经历中挽救疼痛。当前的临床麻醉 由于理解批判性知识差距，在实现这些目标方面没有普遍有效 这些药物如何作用和相互作用的系统级神经科学。 PI是一名物理麻醉师， 生物工程师建立了一个独特而创新的跨学科框架来解决这一重要的 问题。由高级合作者组成的团队，具有心理学专家，功能性MRI分析，MRI工程， 麻醉药理学已经组装了 环境。该项目将确定临床上七个主要机理类别中的麻醉剂如何 使用的代理作用并相互作用以影响认知功能，包括大脑变化的位置。稳定的- 麻醉剂的状态浓度将在高场MRI环境中递送，而受试者执行 精确定时急性疼痛刺激的认知任务；脑电图，电甲型和心脏 节奏数据将简单地获取。包括急性疼痛，使用高场功能性MRI， 与以前的人相比，多模式数据和行为的广泛表征都代表了更严格 麻醉神经科学的工作，并建立在PI最近的研究咪达唑仑和氯胺酮的基础上。第一个计划 项目将完成比较Proposalfol，dexmedetomidine和Fentanyl的机械临床试验，该试验具有 在Pi的K23下开始。这是一项随机安慰剂对照的单盲平行手臂神经成像研究 在健康的成人志愿者中（NCT04062123）。第二组项目将检查利多卡因和Sevoflurane， 完成每个主要机械类别的代表性示例的个人调查 常用的麻醉药。第三组拟议的项目将解决进步的重要障碍 在两个或多个先前表征的机械类别中采用麻醉药的组合。 这将标志着范式的转变，以更现实地模拟临床中无处不在的多功能药物 麻醉练习。麻醉剂的组合将被限制在可行的 在临床实践和选择中，将基于对每个获得的数据的广泛定量分析 代理人进行研究，目的是利用关键的协同行为和神经互动 机械不同的麻醉药。这个系统级神经科学的实体计划的总体目标 研究是为了确定既需要且足以进行麻醉诱导的关键神经签名 抑制记忆形成，恐惧调节和疼痛处理。这将奠定所需的基础 通过更明智的剂量组合，改善临床实践的长期愿景的进步 或增强了术中措施，以确保在麻醉下所有患者的健忘症和镇痛。