The mechanism of axonal injury and regeneration after intrathecal administration of local anesthetics

局麻药鞘内给药后轴突损伤与再生机制

基本信息

批准号：
13671585
负责人：
MATSUMOTO Mishiya
金额：
$ 2.3万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671585/
关键词：
Neurotoxicity local anesthetics glutamate apoptosis oligodendrocyte rabbit 脊椎麻酔脊髄

项目摘要

High concentrations of local anesthetics have been known to be neurotoxic. However, the mechanism for their neurotoxicity Is obscure. We have reported that high concentrations of tetracaine administered intrathecally in the spinal cord increase glutamate concentrations and cause neuronal injury in a dose dependent manner. We investigated whether this is true in other local anesthetics and whether an AMPA receptor antagonist (YM872) can reduce neuronal injury caused by high concentrations of local anesthetics.Lidocaine (10%) , tetracaine (2%), bupivacaine (2%), and ropivacaine (2%) were administered intrathecally at the cauda equina level to the rabbits implanted with an intrathecal microdialysis probe at the lumbar spinal cord level. Glutamate concentrations in the lumbar spinal cord level were monitored by microdialysis. Neurologic and histologic assessment was done one week after the administration. The peak concentrations of glutamate after lidocaine, tetracaine, bupivacaine, and ropivacaine were 10-fold, 6-fold, 5-fold, and 2.5-fold greater than baseline values, respectively. The degree of neuronal injury was in order of lidocaine > tetracaine > bupivacaine > ropivacaine.Intrathecal administration of YM872 tended to reduce sensory and motor function at one week after administration of tetracaine. A chromatolytic change of the motor neuron caused by tetracaine was attenuated by YM872.These results suggest that increased concentrations of glutamate in the cerebrospinal fluid is the common p phenomenon after intrathecal administration of local anesthetics and that glutamate plays, at least in part, an role in the mechanism of neurotoxicity by local anesthetics

众所周知，高浓度的局部麻醉剂是神经毒性的。但是，其神经毒性的机制晦涩难懂。我们报道说，高浓度的四伴临界在脊髓鞘内给药增加了谷氨酸浓度，并以剂量依赖性的方式引起神经元损伤。我们研究了在其他局部麻醉药以及AMPA受体拮抗剂（YM872）是否可以减少由高浓度的局部麻醉剂引起的神经元损伤。Lidocaine.lidocaine（10％），四甲卡因（2％），Bubupivacaine（2％）和Ropivacaine（2％）是Intrath Actath at the Intrath artath artath artath artath artath arthe canectectaimectecaine（YM872）是否会减少神经元损伤。在腰椎脊髓水平上植入鞘内微透析探针。通过微透析监测腰脊髓水平的谷氨酸浓度。神经系统学和组织学评估是在管理后一周进行的。利多卡因，四卡因，布比卡因和ropivacaine之后的谷氨酸的峰浓度分别比基线值大10倍，6倍，5倍和2.5倍。神经元损伤的程度是按照利多卡因>四卡因>布比卡因> ropivacaine的顺序。 YM872抑制了由四甲酸引起的运动神经元的色素变化。这些结果表明，脑脊液中谷氨酸浓度的增加是鞘内服用局部麻醉药后的常见P现象，并且至少在谷氨酸剂中起作用，至少在局部发挥作用，至少在神经毒性中的作用