Background: Local anesthetics have direct neurotoxicity on neurons. However
, precise morphologic changes induced by the direct application of local an
esthetics to neurons have not yet been fully understood. Also, despite the
fact that local anesthetics are sometimes applied to the sites where periph
eral nerves may be regenerating after injury, the effects of local anesthet
ics on growing or regenerating neurons have never been studied.
Methods: Three different neuronal tissues (dorsal root ganglion, retinal ga
nglion cell layer, and sympathetic ganglion chain) were isolated from an ag
e-matched chick embryo and cultured for 20 h. Effects of tetracaine were ex
amined microscopically and by a quantitative morphologic assay, growth cone
collapse assay.
Results: Tetracaine induced growth cone collapse and neurite destruction. T
hree neuronal tissues showed significantly different dose-response, both at
60 min and at 24 h after the application of tetracaine (P < 0.01). The ED5
0 values (mean +/- SD) at 60 min were 1.53 +/- 1.05 mM in dorsal root gangl
ion, 0.15 +/- 0.05 mM in retinal, and 0.06 +/- 0.02 mM In sympathetic gangl
ion chain cultures. The ED50 values at 24 h were 0.43 +/- 0.15 mM in dorsal
root ganglion, 0.07 +/- 0.03 mM in retinal, and 0.02 +/- 0.01 mm in sympat
hetic ganglion chain cultures. Concentration of nerve growth factor in the
culture media did not influence the ED50 values. The growth cone collapsing
effect was partially reversible in dorsal root ganglion and retinal neuron
s. However, in the sympathetic ganglion culture, no reversibility was obser
ved after exposure to 1 mm tetracaine for 10 or for 60 min. Bupivacaine had
similar neurotoxicity to the three types of growing neurons. (The ED50 val
ues at 60 min were 2.32 +/- 0.50 mM in dorsal root ganglion, 0.96 +/- 0.16
m-Ni in retinal, and 0.18 +/- 0.05 mM in sympathetic ganglion chain culture
s. The ED50 values at 24 h were 0.34 +/- 0.09 mM in dorsal root ganglion, 0
.21 +/- 0.06 mM in retinal, and 0.45 +/- 0.10 nm in sympathetic ganglion ch
ain cultures.)
Conclusions: Short-term exposure to tetracaine produced irreversible change
s in growing neurons. Growth cones were quickly affected, and neurites dege
nerated subsequently. Sensitivity varied with neuronal type and was not inf
luenced by the concentration of nerve growth factor. Because a similar phen
omenon was observed after exposure to bupivacaine, the toxicity to growing
neurons may not be unique to tetracaine.