Glutamate release and neuronal injury after intrathecal injection of local anesthetics.
High concentrations of local anesthetics are neurotoxic, but the mechanism for this neurotoxicity is obscure. Here, we report increased concentrations of glutamate in the cerebrospinal fluid after intrathecal injections of high concentrations of tetracaine (a local anesthetic). 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. Animals in the 1% group were all neurologically normal one week after tetracaine injection. In the group receiving 4%, no animal was able to hop and vacuolation of the white matter and/or central chromatolysis of the motor neurons were observed. Because high concentrations of glutamate are known to be neurotoxic, our results may provide some insight into the mechanisms for neurotoxicity of intrathecal local anesthetics.
Ohtake
K
K
Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Japan.
Matsumoto
M
M
Wakamatsu
H
H
Kawai
K
K
Nakakimura
K
K
Sakabe
T
T
D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D007278:Injections, Spinal / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D009498:Neurotoxins / Q000134:cerebrospinal fluid; D011817:Rabbits; D013748:Tetracaine / Q000633:toxicity
D000779:Anesthetics, Local; D009498:Neurotoxins; D013748:Tetracaine; D018698:Glutamic Acid