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Delivery of large doses of local anesthetics for spinal anesthesia by repeated injections or continuous infusion could expose the cauda equina to concentrations of drug that may be neurotoxic per se. We studied this possible neurotoxic effect by assessing recovery from conduction blockade of de-sheathed peripheral nerves after exposure to some of the local anesthetic solutions commonly used for spinal anesthesia.The reversibility of conduction blockade was studied in desheathed bullfrog sciatic nerves, using the sucrose-gap method for recording compound action potentials, before and during exposure to local anesthetics and during drug washout. The nerves were exposed for 15 min to 5% or 1.5% lidocaine, with or without 7.5% dextrose; 0.5% tetracaine; or 0.75% bupivacaine (the latter two without dextrose). Some nerves were also bathed in 7.5% dextrose (without local anesthetic) or in 0.06% tetracaine, which in this preparation is equipotent to 5% lidocaine. After 15 min in the drug, the nerves were washed for 2–3 h and soaked in Ringer's solution overnight. Nerves exposed only to Ringer's solution served as controls. We also studied neuronal uptake and washout of radio-labeled lidocaine.Exposure of nerves to 5% lidocaine, with or without 7.5% dextrose, or to 0.5% tetracaine resulted in irreversible total conduction blockade, whereas 1.5% lidocaine or 0.75% bupivacaine caused 25–50% residual block after the 2–3-h wash. Nerves exposed to Ringer's solution, 7.5% dextrose or 0.06% tetracaine had 0–10% residual block after 2–3 h wash. The action potential of all nerves declined after overnight soak to between 30–60% of the control value, except for those nerves exposed to 5% lidocaine or 0.5% tetracaine, which showed no activity. Exposure to 5% lidocaine for periods of only 4–5 min produced total, irreversible loss of conduction. The uptake by and washout of radiolabeled lidocaine from the nerves indicate that the maximum amount of residual drug after 2–4 min of exposure to 5% lidocaine and a 3-h wash should cause at most only 50% conduction block.Solutions of 5% lidocaine and 0.5% tetracaine that have been associated with clinical cases of cauda equina syndrome after continuous spinal anesthesia caused irreversible conduction block in desheathed amphibian nerve. Whether these in vitro actions also occur in mammalian nerves in vivo is an important, clinically relevant question now under investigation in our laboratory.