Kalichman M W, Powell H C, Myers R R
Department of Anesthesiology, University of California, San Diego.
J Pharmacol Exp Ther. 1989 Jul;250(1):406-13.
Quantitative measurements of endoneurial edema, cytoplasmic lipid droplets, nerve fiber injury and Schwann cell damage were used to elucidate the pathogenesis of local anesthetic-induced injury to sciatic nerve in the rat. All histopathologic measurements were conducted on rat sciatic nerves removed at 48 hr after the extraneural injection of one of three concentrations of the local anesthetic 2-chloroprocaine, procaine, etidocaine or lidocaine. All four drugs produced a concentration-dependent increase in every measure of injury assessed by light microscopy with computer-assisted morphometry of transverse 1-mu thick sections. Edema, lipid inclusions and fiber injury were seen predominantly in the subperineurial region and to a lesser degree in the central areas of nerve fascicles. Quantitative electron microscopic evaluation of Schwann cell injury indicated that the Schwann cells of unmyelinated fibers were more likely to undergo lysis after exposure to local anesthetics, whereas those of myelinated fibers were more likely to accumulate cytoplasmic lipid droplets. These quantitative data on the specificity of the regional distribution of nerve injury and of Schwann cell effects are consistent with a direct cellular toxicity of the local anesthetics; however, these results do not preclude a role for toxicity mediated indirectly by changes in the endoneurial environment.
通过对神经内膜水肿、细胞质脂滴、神经纤维损伤和施万细胞损伤进行定量测量，以阐明局部麻醉药诱导大鼠坐骨神经损伤的发病机制。所有组织病理学测量均在大鼠坐骨神经上进行，这些坐骨神经是在神经外注射三种浓度之一的局部麻醉药2-氯普鲁卡因、普鲁卡因、依替卡因或利多卡因48小时后取出的。通过光学显微镜对1微米厚的横向切片进行计算机辅助形态测量，评估所有四种药物在每种损伤指标上均产生浓度依赖性增加。水肿、脂质包涵体和纤维损伤主要见于神经束膜下区域，在神经束中央区域程度较轻。对施万细胞损伤的定量电子显微镜评估表明，无髓纤维的施万细胞在接触局部麻醉药后更易发生溶解，而有髓纤维的施万细胞更易积累细胞质脂滴。这些关于神经损伤区域分布特异性和施万细胞效应的定量数据与局部麻醉药的直接细胞毒性一致；然而，这些结果并不排除由神经内膜环境变化间接介导的毒性作用。
