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Chronic Exposure to Lidocaine Does Not Alter Flux Through Sodium Channels in Cultured Neuronal Cells
  1. Robert T. Wilder, M.D., Ph.D.*,,
  2. Ravi Chickalingaiah, B.S.§,
  3. Charles B. Berde, M.D., Ph.D.*,,
  4. Gary Strichartz, Ph.D., and
  5. Chauncey T. Griggs, B.S.*
  1. *From Children's Hospital, Boston,
  2. Harvard Medical School, Cambridge,
  3. Brigham and Women's Hospital, Boston, Massachusetts; and
  4. §Dartmouth Medical School, Providence, Rhode Island.
  5. *Instructor in Anaesthesia.
  6. *Associate Professor of Anaesthesia (Pediatrics).
  7. *Research Assistant.
  8. §Medical Student.
  9. Professor of Anaesthesia (Pharmacology).
  1. Address correspondence and reprint requests to Charles B. Berde, M.D., Ph.D., Department of Anesthesia, Farley 3, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115.


Background and Objectives. Although tachyphylaxis to local anesthetics has been reported in the clinical literature for more than two decades,1 the molecular mechanism(s) remain unknown. The authors described an attempt to create an in vitro model for tachyphylaxis to local anesthetics using cultured neuronal cells.

Methods. Murine neuroblastoma cells (N1E115) and rat pheochromocytoma cells (PC-12) were grown in the presence or absence of lidocaine or tetrodotoxin for between 1 and 14 days. Thereafter, the authors tested flux through sodium channels by measuring total and tetrodotoxin-sensitive flux of 14C-labeled guanidinium (a ligand for the sodium channel) into the cells using the technique of Jacques et al.2

Results. Chronic lidocaine or tetrodotoxin treatment caused no change relative to control cells in total or tetrodotoxin-sensitive guanidinium flux, or in the subsequent ability of lidocaine in the flux assay mixture to inhibit guanidinium flux.

Conclusions. The authors concluded that chronic lidocaine or tetrodotoxin application did not produce changes in stimulated sodium channel activity or subsequent lidocaine susceptibility in this model. To the extent that this model simulated the clinical situation, mechanisms other than up-regulation of sodium channel number or maximal stimulated flux per channel may have been responsible for producing tachyphylaxis.

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  • Supported by a grant to the Harvard Anesthesia Center for Research and Teaching, NIH-GM 15904.