BRAIN AND SPINAL CORD CONTRIBUTIONS TO ANESTHETIC ACTION

描述：这是美国国立卫生研究院第一次由一位年轻的研究员提出拨款建议。 为回应计划公告而撰写的PA-96-026，分子 麻醉作用药理学。它的目的是阐明交互作用 脊髓和脑对麻醉效果的贡献。在……里面 在之前的研究中，PI已经提供了脊髓是 吸入剂产生不动的部位，以响应 有害的刺激，大脑的贡献不那么重要，可能 甚至会对抗脊椎的活动。本提案延长了研究的期限。 静脉麻醉剂和镇痛剂对脊髓-大脑相互作用的研究 以及挥发剂，包括异氟醚、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)可以独立灌流，研究人员将 开展研究以(1)确定麻醉剂在大脑中的作用 影响脊髓的伤害性反应和(2)决定如何 脊髓的麻醉作用影响伤害性信息的传递 信息传给大脑。方法包括记录伤害性反应 腰背角、中脑网状结构和中脑网状结构的单个神经元 丘脑，以及伤害性刺激诱发的皮质脑电的变化。 对影响的方向和大小进行了预测 不同的药剂应用于脊髓上的大脑，不同的药剂 适用于背角细胞的躯干，以及不同药剂应用于 躯干将伤害性刺激传递到脊柱上区域。 了解大脑/脊髓在麻醉作用中的关系将 有助于阐明关键终点之间的关系 麻醉，将指导对麻醉机制的进一步研究，并将 导致特定部位的麻醉剂。

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.