LOCAL ANESTHESIA OF PERIPHERAL & CENTRAL NERVE PATHWAYS

末梢局部麻醉

• 批准号: 3288590
• 负责人: GARY R STRICHARTZ
• 金额: $ 31.51万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-02-01 至 1988-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3288590
• 关键词: analgesics; antibody; autoradiography; axon; central nervous system; dorsal root; drug administration routes; drug design /synthesis /production; drug metabolism; electrophysiology; epidural anesthesia; local anesthesia; local anesthetics; mixed tissue /cell culture; neural conduction; neural initiation; neural transmission; neurons; neuropharmacology; neurotransmitters; peripheral nervous system; polymers; radiotracer; single cell analysis; slow release drug; spinal block; spinal ganglion; synapses; tissue /cell culture

The research proposed here expands our effort to establish methods for the selective control of painful sensations using local anesthetics. We plan to elaborate from our present emphasis on axonal phenomena in vitro to record from the peripheral and central projections of neurons in vivo whose physiological role will be identified by unit recording during a spectrum of natural stimuli and motor activities. We will then characterize the actions of anesthetics on these functionally classified nerve fibers using methods developed in our present work. Effects on the CNS of peripheral nerve blocks will be studied by comparing unit responses from the dorsal horn of the spinal cord, and from several mode-selective ascending pathways. The neurophysiological consequences of epidural and intrathecal application of local anesthetics also will be investigated by measuring the relationship between impulses incoming via peripheral nerves, and the responses of spinal units, ventral roots, and centrally projecting pathways. To restrict the diffusion of anesthetic molecules within the spinal cord and epidural space, they will be leashed to macromolecules or synthesized into biologically active polymers. Quaternary amine derivatives of local anesthetics, which inhibit synaptic transmission while sparing axonal conduction, will also be injected intrathecally to help define alternative mechanisms for spinal anesthesia. Recording sites and radioactively-tagged free anesthetics, as well as those leashed to macromolecules or present as polymers, will be localized using light microscopy and radio-autography. To further specify the mechanism of action of anesthetics on spinal neurons we will study such cells in tissue culture by standard intracellular and path-clamp methods, examining the effects of anesthetics and derivatives on single-channel events activated by neuro-transmitters and on transmission between synaptically coupled cells. Studies on isolated peripheral nerve will be extended or physiologically characterized single units further refining the role of changes in pH, pCO2 and temperature on local anesthetic block of functionally characterized fibers.

这里提出的研究扩大了我们的努力，建立方法， 用局部麻醉剂选择性地控制疼痛。 我们计划 从我们目前对体外轴突现象的强调， 来自体内神经元的外周和中枢投射的记录， 生理作用将通过在光谱期间的单位记录来识别 自然刺激和运动活动。 然后我们将描述 麻醉剂对这些功能分类的神经纤维的作用， 在我们目前的工作中开发的方法。 对外周CNS的影响 神经阻滞将通过比较来自背侧的单位反应来研究。 脊髓角，并从几个模式选择性上升 途径。 硬膜外和鞘内麻醉的神经生理学后果 局部麻醉剂的应用也将通过测量 通过外周神经传入的冲动之间的关系， 脊髓单位、前根和中央投射的反应 路径。 为了限制麻醉剂分子在 脊髓和硬膜外腔，它们将被束缚在大分子或 合成生物活性聚合物。 季胺 局部麻醉药的衍生物，其抑制突触传递， 保留轴突传导，也将被注射到鞘内，以帮助 定义脊髓麻醉的替代机制。 记录站点和 放射性标记的自由麻醉剂，以及那些束缚 大分子或作为聚合物存在，将使用光定位 显微镜和放射自显影。 进一步明确麻醉药对脊髓神经元的作用机制 我们将通过标准的细胞内和细胞外培养来研究组织培养中的这些细胞， 路径钳方法，检查麻醉剂和衍生物对 由神经递质激活并传递的单通道事件 在突触耦合细胞之间。 离体周围神经的研究 将进一步扩展或生理表征单个单元 细化pH值，pCO2和温度变化对局部 功能性纤维的麻醉阻滞。