CONTROL OF NEURAL FUNCTION IN ANESTHESIA

描述：修订后的更新提案的主要目标是 建立神经阻滞的药理学条件， 优先感觉或运动障碍，并研究 周围神经纤维的电生理学变化，这些变化的基础 损伤 有三个假设：A.传入冲动在两个 无髓鞘的C“伤害感受器”和有髓鞘的机械敏感性纤维是 引起对有害刺激的退缩反应所必需的; B.输出 中枢（背角）神经元和外周（骨骼肌）的活动 外周轴突冲动的积分器与冲动不成比例 伤害感受器或运动轴突中的频率;和C.局麻药抑制 C-伤害感受器的活性被直接或间接 增加细胞内Ca++，从而修饰TTX不敏感Na+通道。 具体目标有6个：1）用行为分析法鉴定药物， 导致功能选择性缺陷或损害的条件。 （二） 记录功能上确定的传入感觉和 选择性运动中周围神经的传出性轴突 损伤 3)记录伤害性秒电反应的变化 选择性损伤时脊髓背角的有序单位。 4)记录 肌肉对传入外周神经的电反应的变化， 在选择性损害的传出腹根刺激。 5)测量 药物对不同类型心肌细胞Na ~+和K ~+电流的影响 感觉神经元 6)测量外周血中药物的含量和分布 在选择性阻断过程中，在不同的时间对神经进行刺激。 要测试的药物包括传统的局部麻醉剂（利多卡因和 布比卡因）与辣椒素（一种香草素受体激动剂）的组合， 河豚毒素和石房蛤毒素（选择性钠通道拮抗剂），以及 西伐他定和西伐他定（钠通道激活剂）。

DESCRIPTION: The broad objective of this revised renewal proposal is to establish the pharmacological conditions for nerve block that produce preferential sensory or motor impairment in vivo and to investigate the electrophysiological changes in peripheral nerve fibers that underlie these impairments. There are three hypotheses: A. Afferent impulses in both non-myelinated C "nociceptors" and myelinated mechanosensitive fibers are necessary to elicit withdrawal responses to noxious stimuli; B. The output activity of central (dorsal horn) neurons and peripheral (skeletal muscle) integrators of peripheral axon impulses is not proportional to impulse frequency in nociceptors or motor axons; and C. Local anesthetic inhibition of C-nociceptors is potentiated by agents that directly or indirectly increase intracellular Ca++ and thus modify TTX-insensitive Na+ channels. There are 6 specific aims: 1) Identify with behavioral assays the drugs and conditions that give a functionally selective deficit or impairment. 2) Record electrical changes in functionally identified afferent sensory and efferent somato-motor axons in peripheral nerve in situ during selective impairment. 3) Record changes in electrical responses of nociceptive second order units in spinal dorsal horn during selective impairment. 4) Record changes in muscle electrical responses to afferent peripheral nerve and efferent ventral root stimulation during selective impairment. 5) Measure the changes in Na+ and K+ currents induced by drugs in different types of sensory neurons. 6) Measure content and distribution of drugs in peripheral nerve at different times during selective blocking procedures. Drugs to be tested include traditional local anesthetics (lidocaine and bupivacaine) in combination with capsaicin (a vanilloid receptor agonist), tetrodotoxin and saxitoxin (selective sodium channel antagonists), and veratridine and cevadine (sodium channel activators).