LOCAL ANESTHESIA OF PERIPHERAL & CENTRAL NERVE PATHWAYS

在这里提出的研究扩大了我们建立方法的努力 使用局部麻醉剂选择性地控制痛感。我们计划 从我们目前对体外轴突现象的重视到 来自活体神经元外周和中枢投射的记录 生理作用将通过在光谱过程中的单位记录来识别 自然刺激和运动活动。然后，我们将描述 麻醉药对这些功能分类神经纤维的作用 在我们目前的工作中发展的方法。外周对中枢神经系统的影响 将通过比较来自背侧的单位反应来研究神经阻滞。 脊髓的角，并从几个模式选择性上升 小路。硬膜外和鞘内注射对神经生理学的影响 局麻药的应用也将通过测量 通过外周神经传入的冲动与 脊髓单位、前根和中枢投射的反应 小路。限制麻醉剂分子在体内的扩散 脊髓和硬膜外间隙，它们会被绑在大分子或 合成具有生物活性的聚合物。季胺 局麻药的衍生物，它抑制突触传递而 除了轴突传导外，还会在鞘内注入帮助 定义脊椎麻醉的替代机制。录制站点和 放射性标记的游离麻醉剂，以及那些被拴住的麻醉剂 大分子或以聚合物的形式存在，将用光进行定域化 显微镜和无线电自拍。 为了进一步阐明麻醉药对脊髓神经元的作用机制 我们将在组织培养中用标准的细胞内和 路径钳方法，检查麻醉药和衍生物对血管内皮细胞的影响 由神经递质激活的单通道事件和传递 在突触连接的细胞之间。离体外周神经的研究 将扩展或生理特征的单个单位进一步 细化pH、PCO2和温度变化对局部的作用 具有功能特征的纤维的麻醉剂。

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.