BRAIN AND SPINAL CORD CONTRIBUTIONS TO ANESTHETIC ACTION

大脑和脊髓对麻醉作用的贡献

• 批准号: 6180794
• 负责人: JOSEPH ANTOGNINI
• 金额: $ 24.09万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180794
• 关键词: analgesics; anesthesia; anesthetics; behavioral /social science research tag; brain circulation; brain metabolism; cardiovascular pharmacology; cerebral cortex; dorsal horn; drug metabolism; electroencephalography; goats; isoflurane; morphine; neural transmission; neuropharmacology; nitrous oxide; reticular formation; thalamus; thiopental

DESCRIPTION: This is a first NIH grant proposal by a young investigator written in response to the program announcement PA-96-026, Molecular Pharmacology of Anesthetic Action. Its goal is to elucidate the interactive contributions of the spinal cord and brain to anesthetic efficacy. In preceding studies the PI has provided evidence that the spinal cord is the site at which an inhalation agent produces immobility in response to a noxious stimulus, and that cerebral contributions are less important and may even antagonize the spinal actions. The present proposal extends the study of spinal-cerebral interactions to intravenous anesthetic and analgesic agents as well as volatile agents, including isoflurane, nitrous oxide, thiopental, propofol and morphine. In a goat model in which brain and spinal cord (torso) can be independently perfused, the investigator will carry out studies to (1) determine how anesthetic action in the brain influences nociceptive responses in spinal cord and (2) determine how anesthetic action in the spinal cord affects transmission of nociceptive information to the brain. Methods include recording nociceptive responses of single neurons in lumbar dorsal horn, mid-brain reticular formation and thalamus, and changes in cortical EEG evoked by noxious stimulation. Predictions are made about the direction and magnitude of the effects of different agents applied to brain on spinal cord, of different agents applied to torso on dorsal horn cells, and of different agents applied to torso on transmission of nociceptive stimuli to supraspinal areas. Understanding the brain/spinal cord relationship in anesthetic action will contribute to elucidation of the relationship among critical end-points of anesthesia, will guide further research into anesthetic mechanisms, and will lead to site-specific anesthetics.

描述：这是一位年轻研究者提出的第一个 NIH 拨款提案 为回应计划公告 PA-96-026，分子 麻醉作用的药理学。 其目标是阐明交互性 脊髓和大脑对麻醉效果的贡献。 在 PI 之前的研究提供了证据表明脊髓是 吸入剂因响应而产生不动的部位 有害刺激，并且大脑的贡献不太重要，并且可能 甚至对抗脊柱活动。 本提案扩展了研究范围 脊髓-大脑相互作用对静脉麻醉和镇痛的影响 试剂以及挥发性试剂，包括异氟烷、一氧化二氮、 硫喷妥钠、异丙酚和吗啡。 在山羊模型中，大脑和 脊髓（躯干）可以独立灌注，研究者将 进行研究以 (1) 确定大脑中的麻醉作用如何 影响脊髓的伤害性反应，并且 (2) 确定如何 脊髓中的麻醉作用影响伤害性感受的传递 信息传递给大脑。 方法包括记录伤害性反应 腰背角单个神经元、中脑网状结构和 丘脑，以及有害刺激引起的皮质脑电图的变化。 对影响的方向和幅度进行预测 将不同的药物应用于大脑、脊髓、不同的药物 应用于躯干的背角细胞，以及应用于 躯干将伤害性刺激传递到脊柱上区域。 了解麻醉作用中大脑/脊髓的关系将 有助于阐明关键终点之间的关系 麻醉，将指导麻醉机制的进一步研究，并将 导致特定部位麻醉。