Direct neurotoxicity of tetracaine on growth cones and neurites of growingneurons in vitro

S. Saito et al., Direct neurotoxicity of tetracaine on growth cones and neurites of growingneurons in vitro, ANESTHESIOL, 95(3), 2001, pp. 726-733
Citations number
Categorie Soggetti
Aneshtesia & Intensive Care","Medical Research Diagnosis & Treatment
Journal title
ISSN journal
0003-3022 → ACNP
Year of publication
726 - 733
SICI code
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.