The Neurotoxicity of Local Anesthetics on Growing Neurons: A Comparative Study of Lidocaine, Bupivacaine, Mepivacaine, and Ropivacaine
The Neurotoxicity of Local Anesthetics on Growing Neurons: A Comparative Study of Lidocaine, Bupivacaine, Mepivacaine, and Ropivacaine
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DOI：
10.1213/00000539-200202000-00016
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发表时间：
2002-02
影响因子：
5.7
通讯作者：
Inas A. M. Radwan;S. Saito;F. Goto
中科院分区：
文献类型：
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作者：
Inas A. M. Radwan;S. Saito;F. Goto
局部麻醉剂可能具有神经毒性。为了验证暴露于局部麻醉剂产生生长神经元的形态学变化的假设，并比较不同局部麻醉剂之间的神经毒性潜力，我们进行了体外细胞生物学实验与分离的鸡胚背根神经节神经元。利多卡因，布比卡因，甲哌卡因，罗哌卡因的影响进行了检查显微镜和定量评估使用生长锥塌陷试验。我们观察到所有的局麻药引起生长锥塌陷和神经突变性。然而，它们在剂量反应方面表现出显著差异。暴露15分钟时，利多卡因、布比卡因、甲哌卡因和罗哌卡因的IC 50值分别约为10 - 2.8 M、10 - 2.6 M、10 - 1.6 M和10 - 2.5 M。更换培养基后观察到一些可逆性。在洗脱后20小时，布比卡因和罗哌卡因显示出与其对照值相比不显著的生长锥塌陷百分比，而利多卡因和甲哌卡因的生长锥塌陷百分比显著高于对照值。较大浓度的神经生长因子（NGF）并没有改善这种可逆性。总之，局麻药在生长神经元中产生形态学变化，具有显著不同的IC 50。这些变化的可逆性在四种药物之间不同，并且不受NGF浓度的影响。
Local anesthetics can be neurotoxic. To test the hypothesis that exposure to local anesthetics produces morphological changes in growing neurons and to compare this neurotoxic potential between different local anesthetics, we performed in vitro cell biological experiments with isolated dorsal root ganglion neurons from chick embryos. The effects of lidocaine, bupivacaine, mepivacaine, and ropivacaine were examined microscopically and quantitatively assessed using the growth cone collapse assay. We observed that all local anesthetics produced growth cone collapse and neurite degeneration. However, they showed significant differences in the dose response. The IC50 values were approximately, 10−2.8 M for lidocaine, 10−2.6 M for bupivacaine, 10−1.6 M for mepivacaine, and 10−2.5 M for ropivacaine at 15 min exposure. Some reversibility was observed after replacement of the media. At 20 h after washout, bupivacaine and ropivacaine showed insignificant percentage growth cone collapse in comparison to their control values whereas those for lidocaine and mepivacaine were significantly higher than the control values. Larger concentrations of the nerve growth factor (NGF) did not improve this reversibility. In conclusion, local anesthetics produced morphological changes in growing neurons with significantly different IC50. The reversibility of these changes differed among the four drugs and was not influenced by the NGF concentration.