Growth cone collapsing effect of lidocaine on DRG neurons is partially reversed by several neurotrophic factors

Abstract

Background: Local anesthetics were suggested to have a potential for neurotoxicity in both clinical reports and laboratory experiments. Growing neurons have been shown to be susceptible to the toxic effects of local anesthetics in culture. These findings have generated the interest in factors that would rescue the neurons affected by the neurotoxicity of local anesthetics. Methods: Primary cultured dorsal root ganglia were isolated from age-matched chick embryos and exposed to lidocaine. After 60 min of exposure, the culture media were replaced to wash out the lidocaine. Neurotrophic factors (NTFs) - brain-derived neurotrophic factor, glial-derived neurotrophic factor, or neurotrophin 3 - were added to the replacement media to examine the capacity of these NTFs to support the reversibility of the lidocaine-induced growth cone collapse. The growth cone collapse assay was applied a quantitative method of assessment. Results: When any of the three NTFs was added to the replacement media at a minimum concentration of 10 ng/ml, significantly high reversibility of the lidocaine-induced growth cone collapse was observed, especially at 48 h after washout (P < 0.05). At that time point, there was no significant difference between the values of growth cone collapse percentage in the cells that were exposed to lidocaine and supported by the NTFs after the washout, and the control cells (not exposed to lidocaine) (P > 0.05). Conclusion: The NTFs - brain-derived neurotrophic factor, glial-derived neurotrophic factor, and neurotrophin 3 - were demonstrated to support the reversibility of lidocaine-induced growth cone collapse in primary cultured sensory neurons, an effect that was concentration- and time-dependent. Because similar effects were observed after tetracaine washout, the supporting effects of NTFs may not be specific to lidocaine.