The mechanism for neurotoxicity of local anesthetics

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High concentrations of local anesthetics have been known to be neurotoxic. However, the mechanism for its neurotoxicity is obscure. We investigated the effect of local anesthetics with or without epinephrine injected intrathecally in the lumbar spinal cord on the concentrations of glutamate in the cerebrospinal fluid and neuronal injury.Tetracaine (0.3 mL) was 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 cerebrospinal fluid were monitored by microdialysis. Neurologic and histopathologic assessments were done one week after the administration. Tetracaine increased glutamate concentrations in a dose-dependent manner. The peak concentrations of glutamate after administration of 1%, 2%, and 4% tetracaine were 4-fold, 6-fold, and 10-fold higher than baseline values, respectively. Addition of epinephrine (0.1 mg/mL) to tetracaine did not augment the peak concentrations of glutamate but sustained high concentrations of glutamate. Animals given 1% tetracaine were all neurologically normal. No animal given 4% tetracaine was able to hop. Characteristic histologic changes in animals with sensory and motor dysfunction were vacuolation in the dorsal funiculus and chromatolytic damagc of motor neurons in the lumbar spinal cord. The vacuolation of the dorsal funiculus was worsened by the addition of epinephrine to tetracaine.These results suggest that increased concentrations of glutamate in the cerebrospinal fluid may possibly be related to the mechanism for neurotoxicity of local anesthetics and that addition of epinephrine to tetracaine may inerease its neurotoxicity.