Effects of anesthesia related drugs on neuronal apoptosis : alterations of enzymatic activities elicited by intracellular calcium elevation.

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Local anesthetics impair morphology of neurons and disturb physiological nerve conduction. Especially, lidocaine and tetracaine are most toxic among the commercially available local anesthetics. Apoptosis is one of the basic mechanism of the neurotoxity, however, recent publications described that the toxicity could not be thoroughly explained by apoptosis. Growth cones at the tip of growing neurons have been demonstrated as labile to the neurotoxicity of local anesthetics. Several neurotrophic factors promote the recovery of neurons that are exposed to local anesthetics. In the present study, we have demonstrated that mepivacaine, bupivacaine and ropivacaine have similar neurotoxity to growth cones and growing neurites, and that neurotrophic factors, NT-3, BDNF, GDNF, have potential to promote neuronal survival and regeneration following the injury by local anesthetics. Intracellular calcium ion elevation was observed after the exposure to tetracaine beginning from the tip of growing neurite. The way of elevation was not spiky but slowly elevating, and implied impairment of membrane integrity.