Powell H C, Kalichman M W, Garrett R S, Myers R R
Veterans Administration Research Service, San Diego, La Jolla, California.
Lab Invest. 1988 Aug;59(2):271-80.
When peripheral nerves of experimental rats are exposed to local anesthetics, distinctive and reproducible pathologic changes occur involving the perineurial sheath and endoneurial contents. Application of intermediate strength concentrations of the local anesthetics, 2-chloroprocaine, lidocaine, etidocaine, and intermediate or high concentrations of procaine to the surface of rat sciatic nerves resulted in the following changes. By 48 hours, the perineurial sheath exposed to the drug was disrupted and became permeable to granulocytes which infiltrated the subjacent endoneurium in conjunction with edema formation in the endoneurial interstitium. Application of 10% procaine to exposed nerve resulted in extensive demyelination. The most striking pathologic change occurring with either intermediate or high doses was accumulation of lipid droplets in Schwann cells, a phenomenon that occurred often in myelin-producing Schwann cells but much less frequently in unmyelinated fiber Schwann Cells. Lipid accumulation appears to be one of several reactive changes that affect Schwann cells of myelinated fibers and is dose-dependent. On the other hand, while reactive changes were infrequently seen in unmyelinated fiber Schwann cells, these cells appeared more susceptible to injury as shown by electron microscopy. Injury to Schwann cells by local anesthetics is temporary because these cells can replicate quickly. Autoradiographic studies of thymidine incorporation 1 week after procaine administration to the sciatic nerve showed intense proliferation of Schwann cells, but no such activity in controls. These findings support the view that their neurotoxic properties may account in some part for the function of local anesthetics, that Schwann cells of small unmyelinated fibers are more vulnerable to these agents than those of myelinated fibers, and that destruction of their supporting cells is followed by vigorous mitotic activity in the endoneurium.
当将实验大鼠的外周神经暴露于局部麻醉剂时，会出现涉及神经束膜和神经内膜内容物的独特且可重复的病理变化。将中等强度浓度的局部麻醉剂（2-氯普鲁卡因、利多卡因、依替卡因）以及中等或高浓度的普鲁卡因应用于大鼠坐骨神经表面会导致以下变化。到48小时时，暴露于药物的神经束膜被破坏，对粒细胞变得通透，粒细胞与神经内膜间质中的水肿形成一起浸润下方的神经内膜。将10%的普鲁卡因应用于暴露的神经会导致广泛的脱髓鞘。中等剂量或高剂量时出现的最显著病理变化是施万细胞中脂滴的积累，这种现象在产生髓磷脂的施万细胞中经常发生，但在无髓纤维施万细胞中较少见。脂滴积累似乎是影响有髓纤维施万细胞的几种反应性变化之一，且呈剂量依赖性。另一方面，虽然在无髓纤维施万细胞中很少见到反应性变化，但电子显微镜显示这些细胞似乎更容易受到损伤。局部麻醉剂对施万细胞的损伤是暂时的，因为这些细胞能够快速复制。对坐骨神经给予普鲁卡因1周后进行的胸腺嘧啶核苷掺入的放射自显影研究显示施万细胞有强烈增殖，但对照组无此活性。这些发现支持以下观点：局部麻醉剂的神经毒性特性可能在一定程度上解释了其功能；小的无髓纤维的施万细胞比有髓纤维的施万细胞更容易受到这些药物的影响；其支持细胞被破坏后，神经内膜会有活跃的有丝分裂活动。
