CHRONIC EXPOSURE TO LIDOCAINE DOES NOT ALTER FLUX THROUGH SODIUM-CHANNELS IN CULTURED NEURONAL CELLS

Background and Objectives. Although tachyphylaxis to local anesthetics has been reported in the clinical literature for more than two decade s,1 the molecular mechanism(s) remain unknown. The authors described a n attempt to create an in vitro model for tachyphylaxis to local anest hetics using cultured neuronal cells. Methods. Murine neuroblastoma ce lls (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 m easuring total and tetrodotoxin-sensitive flux of C-14-labeled guanidi nium (a ligand for the sodium channel) into the cells using the techni que of Jacques et al.2 Results. Chronic lidocaine or tetrodotoxin trea tment caused no change relative to control cells in total or tetrodoto xin-sensitive guanidinium flux, or in the subsequent ability of lidoca ine in the flux assay mixture to inhibit guanidinium flux. Conclusions . The authors concluded that chronic lidocaine or tetrodotoxin applica tion 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 cha nnel may have been responsible for producing tachyphylaxis.