Membrane effect of lidocaine is inhibited by interaction with peroxynitrite

Inflammation is clinically well known to decrease the efficiency of local anesthesia, an effect which has been explained mechanistically by tissue acidosis in the literature. However, recent studies offer no support to such a pharmacopathological background for anesthetic failure. Because inflammatory cells produce significant amounts of peroxynitrite, the peroxynitrite could interact with local anesthetics to decrease their effects. To examine this speculated interaction, we determined whether membrane fluidization, as one mode of local anesthetic action, was influenced by peroxynitrite. The membrane effects were analyzed by measuring the fluorescence polarization of liposomes prepared with 1, 2-dipalmitoylphosphatidylcholine. Although lidocaine, at a clinically relevant concentration, fluidized liposomal membranes, its fluidizing potency was reduced to 43.6 +/- 4.4% and 58.4 +/- 7.5% of that in membranes without peroxynitrite when membranes were pretreated with 50 and 250 microM peroxynitrite, respectively, for 15 min. A significant inhibition of membrane fluidization of 27.5 +/- 6.8%, was also observed after reaction for 5 min. Peroxynitrite released by inflammatory cells may affect local anesthesia through a possible interaction with lidocaine, inhibiting its membrane-fluidizing effect.