title: Despite differences in cytosolic calcium regulation, lidocaine toxicity is similar in adult and neonatal rat dorsal root ganglia in vitro.
abstract: BACKGROUND
  Neuraxial local anesthetics may have neurological complications thought to be due to neurotoxicity. A primary site of action of local anesthetics is the dorsal root ganglia (DRG) neuron. Physiologic differences have been noted between young and adult DRG neurons; hence, the authors examined whether there were any differences in lidocaine-induced changes in calcium and lidocaine toxicity in neonatal and adult rat DRG neurons.
  
  
  METHODS
  DRG neurons were cultured from postnatal day 7 (P7) and adult rats. Lidocaine-induced changes in cytosolic calcium were examined with the calcium indicator Fluo-4. Cells were incubated with varying concentrations of lidocaine and examined for viability using calcein AM and ethidium homodimer-1 staining. Live imaging of caspase-3/7 activation was performed after incubation with lidocaine.
  
  
  RESULTS
  The mean KCl-induced calcium transient was greater in P7 neurons (P < 0.05), and lidocaine significantly inhibited KCl-induced calcium responses in both ages (P < 0.05). Frequency distribution histograms of KCl-evoked calcium increases were more heterogeneous in P7 than in adult neurons. With lidocaine, KCl-induced calcium transients in both ages became more homogeneous but remained different between the groups. Interestingly, cell viability was decreased by lidocaine in a dose-dependent manner similarly in both ages. Lidocaine treatment also activated caspase-3/7 in a dose- and time-dependent manner similarly in both ages.
  
  
  CONCLUSIONS
  Despite physiological differences in P7 and adult DRG neurons, lidocaine cytotoxicity is similar in P7 and adult DRG neurons in vitro. Differences in lidocaine- and KCl-evoked calcium responses suggest the similarity in lidocaine cytotoxicity involves other actions in addition to lidocaine-evoked effects on cytosolic calcium responses.
authors.affiliation: From the Department of Anesthesiology, New York University School of Medicine, New York, New York.
authors.forename: Lisa V
authors.initials: LV
authors.lastname: Doan
authors.forename: Olga
authors.initials: O
authors.lastname: Eydlin
authors.forename: Boris
authors.initials: B
authors.lastname: Piskoun
authors.forename: Richard P
authors.initials: RP
authors.lastname: Kline
authors.forename: Esperanza
authors.initials: E
authors.lastname: Recio-Pinto
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rosenberg
authors.forename: Thomas J J
authors.initials: TJ
authors.lastname: Blanck
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
mesh_terms: D000375:Aging / Q000502:physiology*; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005727:Ganglia, Spinal / Q000473:pathology*; D008012:Lidocaine / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000779:Anesthetics, Local; D011189:Potassium Chloride; D008012:Lidocaine; D053148:Caspase 3; D053179:Caspase 7; D002118:Calcium