抄録
Intrathecal administration of lidocaine primarily causes degeneration of the dorsal root in rats. To determine membrane mechanisms of neurotoxicity of lidocaine, the lidocaine-induced impairment of axonal transport in cultured mouse dorsal root ganglion neurons was investigated. Lidocaine (1-100 mM) inhibited axonal transport in a time- and dose-dependent manner. Higher concentrations (50-100 mM) of lidocaine caused membrane rupture and cell death. Ca2+-free solution and the Ca2+-calmodulin kinase II (CAM kinase II) inhibitor KN-62 reduced the inhibition of axonal transport but not membrane rupture. Lysophosphatidic acid, a bioactive phospholipid, blocked both the inhibition of axonal transport and membrane rupture. Thus, lidocaine at lower concentrations (<10 mM) may form pores in the membrane, resulting in Ca2+ influx and activation of CAM kinase II to inhibit axonal transport. Neurotoxic effect of higher concentrations of lidocaine seems to be a direct disruption of cell membrane. Lysophosphatidic acid may be useful to prevent neurotoxocity of lidocaine even at higher concentrations. [Jpn J Physiol 54 Suppl:S70 (2004)]
