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

• 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

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

已知高浓度的局部麻醉剂具有神经毒性。然而，它们的神经毒性机制尚不清楚。我们报道，脊髓鞘内注射高浓度丁卡因会增加谷氨酸浓度，并以剂量​​依赖性方式引起神经元损伤。我们研究了其他局麻药是否也是如此，以及 AMPA 受体拮抗剂 (YM872) 是否可以减少高浓度局麻药引起的神经元损伤。利多卡因 (10%)、丁卡因 (2%)、布比卡因 (2%) 和对植入鞘内微透析探针的兔子，在马尾水平鞘内注射罗哌卡因 (2%)。腰脊髓水平。通过微透析监测腰脊髓水平的谷氨酸浓度。给药后一周进行神经学和组织学评估。利多卡因、丁卡因、布比卡因和罗哌卡因后谷氨酸的峰值浓度分别比基线值高10倍、6倍、5倍和2.5倍。神经元损伤程度依次为利多卡因>丁卡因>布比卡因>罗哌卡因。鞘内注射YM872在丁卡因给药1周后有感觉和运动功能下降的趋势。 YM872 减弱了丁卡因引起的运动神经元的染色质变化。这些结果表明，鞘内注射局部麻醉药后，脑脊液中谷氨酸浓度增加是常见的现象，并且谷氨酸至少在一定程度上发挥了作用局麻药神经毒性机制

项目成果

Yamashita A., Matsumoto M., et al.: "A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits"Anesthesia & Analgesia. in press.

Yamashita A.、Matsumoto M. 等人：“兔鞘内注射丁卡因、利多卡因、布比卡因和罗哌卡因对脊髓的神经毒性作用的比较”

Yamashita A, Matsumoto M, et al.: "A comparison of the neurotoxic effects on the spinal cord of tetracaine, lidocaine, bupivacaine, and ropivacaine administered intrathecally in rabbits"Anesthesia & Analgesia. (in press).

Yamashita A、Matsumoto M 等人：“兔鞘内注射丁卡因、利多卡因、布比卡因和罗哌卡因对脊髓的神经毒性作用的比较”