BRAIN AND SPINAL CORD CONTRIBUTIONS TO ANESTHETIC ACTION

描述：这是一位年轻的研究者提出的第一份NIH拨款申请。 为响应计划公告PA-96-026，分子 麻醉作用药理学。 它的目标是阐明互动 脊髓和大脑对麻醉效果的贡献。 在 先前的研究PI提供的证据表明，脊髓是 吸入剂在其处响应于 有害刺激，大脑的贡献不太重要，可能 甚至对抗脊髓的活动。 目前的建议扩大了研究范围， 脊髓-大脑相互作用对静脉麻醉剂和镇痛剂的影响 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， 脊髓（躯干）可以独立灌注，研究者将 开展研究，以（1）确定麻醉剂在大脑中的作用 影响脊髓中的伤害性反应和（2）确定如何 脊髓中的麻醉作用影响伤害性感受的传递 信息到大脑。 方法包括记录伤害性反应 腰后角、中脑网状结构和 丘脑和皮层脑电图的变化引起的伤害性刺激。 预测的方向和规模的影响， 应用于脑脊髓的不同药剂，不同药剂 应用于躯干的背角细胞，以及应用于 躯干对传递伤害性刺激到脊髓上区域的影响。 了解麻醉作用中的脑/脊髓关系将 有助于阐明关键终点之间的关系， 麻醉，将指导进一步研究麻醉机制，并将 从而导致部位特异性麻醉剂。

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.