Possible Mechanism of Irreversible Nerve Injury Caused by Local Anesthetics

Abstract

Background Irreversible nerve injury may result from neural membrane lysis due to the detergent properties of local anesthetics. This study aimed to investigate whether local anesthetics display the same properties as detergents and whether they disrupt the model membrane at high concentrations. Methods Concentrations at which dodecyltrimethylammonium chloride and four local anesthetic (dibucaine, tetracaine, lidocaine, and procaine) molecules exhibit self-aggregation in aqueous solutions were measured using an anesthetic cation-sensitive electrode. Light-scattering measurements in a model membrane solution were also performed at increasing drug concentrations. The concentration at which drugs caused membrane disruption was determined as the point at which scattering intensity decreased. Osmotic pressures of anesthetic agents at these concentrations were also determined. Results Concentrations of dodecyltrimethylammonium chloride, dibucaine, tetracaine, lidocaine, and procaine at which aggregation occurred were 0.15, 0.6, 1.1, 5.3, and 7.6%, respectively. Drug concentrations causing membrane disruption were 0.09% (dodecyltrimethylammonium chloride), 0.5% (dibucaine), 1.0% (tetracaine), 5.0% (lidocaine), 10.2% (procaine), and 20% (glucose), and osmotic pressures at these concentrations were 278, 293, 329, 581, 728, and 1,868 mOsm/kg H2O, respectively. Conclusions These results show that all four local anesthetics form molecular aggregations in the same manner as dodecyltrimethylammonium chloride, a common surfactant. At osmotic pressures insufficient to affect the membrane, local anesthetics caused membrane disruption at the same concentrations at which molecular aggregation occurred. This shows that disruption of the model membrane results from the detergent nature of local anesthetics. Nerve membrane solubilization by highly concentrated local anesthetics may cause irreversible neural injury.