title: Glutamate release and neurologic impairment after intrathecal administration of lidocaine and bupivacaine in the rat.
abstract: BACKGROUND
  Local anesthetic-induced neurotoxicity is one of the potential causes of postspinal anesthesia neurologic injury. Many experimental and clinical studies have demonstrated that lidocaine is more neurotoxic than bupivacaine. The mechanisms of local anesthetic-induced neurotoxicity remain unclear. Glutamate is an excitatory amino acid and widely exists in the central nervous system. Overstimulation of the glutamate receptors may produce neuronal toxic effect. In this study, we used in vivo microdialysis to examine the glutamate release in cerebrospinal fluid (CSF) after intrathecal lidocaine and bupivacaine injection.
  
  
  METHODS
  Male Wistar rats were used. Administration of lidocaine (5 groups: normal saline, 2.5%, 5%, 10%, and 10% + MK-801 intrathecally injected) and bupivacaine (4 groups: normal saline, 0.25%, 0.5%, and 1% intrathecally injected) was performed in both microdialysis and postinjection neurologic sequelae studies. After intrathecal injection of the studied agents, the CSF dialysates were collected in 10-minute intervals for 2 hours. Cerebrospinal fluid glutamate concentrations were measured by high-performance liquid chromatography. In addition, tail-flick latencies were examined daily before and after microdialysis for 4 days.
  
  
  RESULTS
  Intrathecal lidocaine concentration-dependently elevated glutamate release in CSF. Pretreatment with MK-801 significantly inhibited the glutamate release induced by 10% lidocaine. Intrathecal bupivacaine has no influence on glutamate release in CSF. The tail-flick latencies were significantly prolonged for 4 days after intrathecal lidocaine injection, and these effects were in a concentration-dependent manner. Pretreatment with MK-801 significantly reversed the 10% lidocaine-induced prolonged tail-flick latencies. There was no difference of the tail-flick latencies among the bupivacaine-treated groups.
  
  
  CONCLUSIONS
  Intrathecal lidocaine caused a concentration-dependent increase of the CSF glutamate release and postinjection neurologic impairment; these effects can be reversed by MK-801. However, intrathecal bupivacaine shows no influence. We suggest that glutamate may be involved in the pathogenesis of lidocaine-induced spinal neurotoxicity.
authors.affiliation: Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan. cherng1018@yahoo.com.tw
authors.forename: Chen-Hwan
authors.initials: CH
authors.lastname: Cherng
authors.forename: Chih-Shung
authors.initials: CS
authors.lastname: Wong
authors.forename: Ching-Tang
authors.initials: CT
authors.lastname: Wu
authors.forename: Chun-Chang
authors.initials: CC
authors.lastname: Yeh
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage* / Q000633:toxicity; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D017551:Microdialysis / Q000379:methods; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
chemical_list: D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D008012:Lidocaine; D002045:Bupivacaine