Effect of Local Anesthetic on Neuronal Cytoplasmic Calcium and Plasma Membrane Lysis (Necrosis) in a Cell Culture Model

Abstract

In this model, lidocaine greater than 2.5% elevates Ca2+(cyt) to toxic levels. Bupivacaine and lower concentrations of lidocaine transiently alter Ca2+(cyt) homeostasis for several minutes, but without an immediate neurotoxic effect within 60 min.

Trigeminal nerve injuries in relation to the local anaesthesia in mandibular injections

“…Certainly increasing the local anaesthetic concentration increases neurotoxicity in vitro. 23 The studies of Haas and Lennon, 1 Hillerup and Jensen 13 and Gaffen and Haas 24 suggest that more concentrated 4% solutions are more likely to produce damage, however others 12,25 dispute this, pointing out that the nerve most often damaged is the lingual nerve and the solution is more usually deposited closer to the inferior alveolar nerve during an IAN block. Although there are insufficient data in the present study related to the types of LA used in the study population to inform the debate about the effect of concentration, it is apparent from the results that nerve damage is not exclusively caused by higher concentrations of solutions.…”

Local Anesthetics

“…The reasons underlying this difference are not known, and the sensitivity of other TRP channels to local anesthetics have not been investigated. Intracellular Ca 2+ is elevated by many local anesthetics in several types of cells (Gold et al 1998b;Johnson et al 2002), very possibly through their ability to uncouple mitochondria and thereby release this organelle's stored Ca 2+ into the cytoplasm (Chance et al 1968(Chance et al , 1969. Consequently, a number of Ca 2+ -dependent processes are stimulated by local anesthetics, including calmodulin-dependent reactions that turn on kinases and inactivate Ca 2+ channels.…”

“…The most probable mechanism for these events, which often manifest clinically as cauda equina syndrome, probably due to a loss of functions mediated by lower lumbar and sacral nerve roots, is an irreversible conduction block of these roots (Adams et al 1974;Ready et al 1985;Schell et al 1991;Lambert and Hurley 1991). Exposure of isolated peripheral nerve to high concentrations of lidocaine acutely results in such irreversible blockade (Lambert et al 1994;Bainton and Strichartz 1994) and also induces death of neurons isolated from rat dorsal root ganglia (Gold et al 1998b;Johnson et al 2002).…”

“…Although some neuronal Ca 2+ channels are inhibited by LAs (see Sect. 2.3, above), the lidocaine-induced increase in intracellular Ca 2+ appears to be the mechanism of lidocaine-induced neuronal toxicity (Gold et al 1998b;Johnson et al 2002). Samples of human CSF taken 5 min after administration of a 5% (∼200 mM) solution of lidocaine revealed a mean cerebrospinal drug concentration close to 16 mM (Van Zundert et al 1996).…”

“…In contrast to apoptosis, necrosis is characterized by a rapid swelling of the cell and its subsequent lysis, with random degradation of DNA (Wyllie et al 1980). Chloroprocaine has been shown to induce Schwann cell necrosis in rat peripheral nerve bundle exposed to this LA in vivo several days beforehand (Myers et al 1986), and in cultured cells local anesthetics elevate cytoplasmic Ca 2+ to toxic levels to induce plasma membrane lysis and death (necrosis; Joshi et al 1999;Johnson et al 2002).…”