ANESTHETIC EFFECTS ON SENSORIMOTOR INTEGRATION

麻醉对感觉运动整合的影响

• 批准号: 7029796
• 负责人: JOSEPH ANTOGNINI
• 金额: $ 19.09万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7029796
• 关键词: anesthesia; anesthetics; brain regulatory center; decerebration; dorsal horn; dosage; drug adverse effect; drug screening /evaluation; evoked potentials; gene expression; halothane; immunocytochemistry; isoflurane; laboratory rat; motor neurons; nociceptors; protooncogene; sensorimotor system; stimulus /response; tissue /cell culture

DESCRIPTION (provided by applicant): Recent evidence supports the notion that the spinal cord is the site where anesthetics suppress movement resulting from noxious stimuli. While gains have been made in our understanding of specific neurotransmitter receptors that are modulated by anesthetics, we lack understanding of these anesthetic actions at an integrative level-e.g., at which spinal cord locations and types of neurons do anesthetic effects interact to produce immobility? To shed light on anesthetic effects on sensorimotor processing, the present proposal will use neurophysiological methods to assess the effects of isoflurane (ISO), halothane (HAL) and propofol (PROP) at several spinal sites (dorsal horn; intermediate and ventral horn) and on anatomically or functionally different neuronal types (wide-dynamic range, nociceptive specific neurons, sensory neurons with ascending projections, pre-motor interneurons). In Aim 1 we will test the hypothesis that anesthetics differ in their effects on neurons at different depths in the spinal cord. We hypothesize that ISO will have predominant effects at ventral spinal cord sites, whereas HAL and PROP will have effects on both dorsal and ventral spinal cord sites. In Aim 2 we will test the hypothesis that neurons with ascending projections (such as spinothalamic neurons) are more sensitive to anesthetics as compared to local segmental neurons. Furthermore, in Aim 2, we will test the hypothesis that wide-dynamic range neurons are more resistant to anesthesia compared to nociceptive specific neurons. In Aim 3, we will test the hypothesis that GABA-A antagonism (picrotoxin), glycine antagonism (strychnine) and glutamate agonism (NMDA) will reverse anesthetic depression of spinal cord neuronal function in an anesthetic-specific way, with GABA antagonism being more specific for PROP and glutamate and glycine antagonism being more specific for ISO and HAL. The results will lead to a better understanding of how anesthetics modulate neuronal function at an integrative systems level. Understanding how and where anesthetics act will eventually lead to the development of better and safer anesthetics, thereby decreasing peri-operative morbidity and mortality and improving public health.

描述（由申请人提供）：最近的证据支持这样一种观点，即脊髓是麻醉剂抑制有害刺激引起的运动的部位。虽然我们对麻醉剂调节的特定神经递质受体的理解已经取得了进展，但我们缺乏对这些麻醉作用在综合水平上的理解。，在脊髓的哪些位置和类型的神经元，麻醉作用相互作用产生不动？为了阐明麻醉对感觉运动加工的影响，本研究将使用神经生理学方法来评估异氟烷（ISO）、氟烷（HAL）和异丙酚（PROP）对几个脊柱部位（背角、中间角和腹角）以及解剖或功能上不同的神经元类型（宽动态范围、伤害性特异性神经元、上升投射的感觉神经元、运动前中间神经元）的影响。在Aim 1中，我们将测试麻醉药对脊髓不同深度神经元的影响不同的假设。我们假设ISO将主要作用于脊髓腹侧部位，而HAL和PROP将同时作用于脊髓背侧和腹侧部位。在Aim 2中，我们将验证具有上升投射的神经元（如脊髓丘脑神经元）比局部节段神经元对麻醉剂更敏感的假设。此外，在Aim 2中，我们将验证宽动态范围神经元比伤害性特异性神经元对麻醉更有抵抗力的假设。在Aim 3中，我们将检验GABA- a拮抗剂（picrotoxin）、甘氨酸拮抗剂（士的宁）和谷氨酸激动剂（NMDA）以麻醉特异性的方式逆转脊髓神经元功能的麻醉抑制的假设，其中GABA拮抗剂对PROP更特异性，而谷氨酸和甘氨酸拮抗剂对ISO和HAL更特异性。该结果将有助于更好地理解麻醉药如何在综合系统水平上调节神经元功能。了解麻醉药如何以及在何处起作用将最终导致更好和更安全的麻醉药的发展，从而降低围手术期的发病率和死亡率，改善公众健康。