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首页> 外文学位 >Central and peripheral analgesic properties of local anesthetics: Effects of lidocaine on thalamic neurons and efficacy of ropivacaine in femoral 3-in-1 nerve blockade.
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Central and peripheral analgesic properties of local anesthetics: Effects of lidocaine on thalamic neurons and efficacy of ropivacaine in femoral 3-in-1 nerve blockade.

机译：局麻药的中枢和外周镇痛特性：利多卡因对丘脑神经元的影响和罗哌卡因在股三合一神经阻滞中的功效。

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摘要

This thesis is dedicated to the pharmacology & therapeutics of local anesthetics, with a specific focus on their analgesic properties.; The specific objective of the laboratory studies was to define the concentration-dependent effects of lidocaine on the membrane properties and excitability of neurons in the ventral posterior lateral thalamic nucleus (VPL), a major somatosensory and nociceptive relay station that plays a central role in pain states. Lidocaine produces central analgesia and sedation when present in the systemic circulation at low concentrations, and evidence implicates VPL neurons in these actions. Differential interference contrast infrared (DIC-IR) videomicroscopy-guided whole-cell patch clamp techniques were used to record from VPL neurons in rat brain slice preparations. Low, analgesic lidocaine concentrations (10 muM) significantly decreased neuronal input resistance (R i), which shunted action potentials, increased current thresholds, and reduced tonic firing. The effects were not associated with the classic signs of Na+ conductance blockade. The GABAA receptor antagonist, bicuculline, had no effect on the lidocaine-induced shunt. Higher lidocaine concentrations (≥300 muM; clinically CNS-toxic) did not decrease Ri but reversibly unmasked high threshold Ca2+ spikes (HTSs), susceptible to blockade by Cd2+. Extracellular QX-314, a quaternary lidocaine analogue, increased rather than decreased Ri. Similarly, neither procainamide nor bupivacaine reduced Ri. In summary, these studies identified novel actions of lidocaine in the thalamus, distinct from the classic effects on Na + conductance. The observation of an unmasking of high threshold Ca 2+ spikes is in contrast to previous studies in other tissues showing that lidocaine blocks Ca2+ conductances, and is of potential significance for the mechanisms of local anesthetic CNS toxicity.; The purpose of the clinical studies was to test if postoperative pain control in patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR) under general anesthesia is improved by addition of a preincisional femoral 3-in-1 block with ropivacaine 0.2% to standard intra-articular instillation at the end of surgery. In a prospective, randomized, controlled, double-blind trial (RCT), 44 patients scheduled for inpatient ACLR were studied. In conclusion, the clinical studies demonstrated no significant effect in an RCT of a femoral 3-in-1 block with ropivacaine 0.2% on postoperative analgesic consumption, compared to intra-articular instillation alone, in patients undergoing ACLR under general anesthesia. (Abstract shortened by UMI.)
机译：本论文致力于局部麻醉药的药理学和治疗学，特别关注其镇痛作用。实验室研究的特定目标是确定利多卡因对腹侧后外侧丘脑核（VPL）的膜特性和神经元兴奋性的浓度依赖性作用，腹侧后丘脑外侧核（VPL）是主要的体感和伤害感受性中继站，在疼痛中起主要作用状态。当利多卡因以低浓度存在于全身循环中时，会产生中枢镇痛和镇静作用，并且证据表明VPL神经元参与了这些作用。差分干涉对比红外（DIC-IR）视频显微镜引导的全细胞膜片钳技术被用于记录大鼠脑切片制剂中的VPL神经元。镇痛剂利多卡因的低浓度（10μM）显着降低了神经元输入阻力（R i），这使动作电位分流，电流阈值增加和滋补生火减少。这些影响与Na +电导阻滞的经典迹象无关。 GABAA受体拮抗剂bicuculline对利多卡因诱导的分流没有影响。更高的利多卡因浓度（≥300μM；临床上对中枢神经系统有毒）不会降低Ri，但可逆地掩盖高阈值Ca2 +尖峰（HTSs），容易被Cd2 +阻断。细胞外QX-314是一种四级利多卡因类似物，其Ri增加而不是减少。同样，普鲁卡因酰胺和布比卡因均不能降低Ri。总之，这些研究确定了利多卡因在丘脑中的新作用，这与对Na +电导的经典作用不同。高阈值Ca 2+尖峰未掩盖的观察与先前在其他组织中的研究相反，后者表明利多卡因会阻断Ca2 +电导，并且对局麻CNS毒性机制具有潜在意义。临床研究的目的是测试在全麻下进行关节镜前交叉韧带重建术（ACLR）的患者的术后疼痛控制是否通过在标准关节内添加0.2％罗哌卡因的术前股骨三合一阻滞剂得到改善手术结束时滴注。在一项前瞻性，随机，对照，双盲试验（RCT）中，研究了计划入院ACLR的44例患者。总之，与仅进行关节腔内滴注相比，在全身麻醉下接受ACLR的患者，临床研究表明，与单独的关节腔内滴注相比，含0.2％罗哌卡因的股骨3合1阻滞剂的RCT对术后镇痛剂的消耗没有显着影响。 （摘要由UMI缩短。）

著录项

  • 作者

    Schwarz, Stephan Karl Walter.;

  • 作者单位

    The University of British Columbia (Canada).;

  • 授予单位 The University of British Columbia (Canada).;
  • 学科 Biology Neuroscience.; Health Sciences Pharmacology.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 171 p.
  • 总页数 171
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;药理学;
  • 关键词

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