Effects of Local Anesthetics on Nerve Growth in Culture

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Abstract
The effects of the tertiary amine local anesthetics, procaine, lidocaine, and tetracaine, on 8-day-old chick embryo dorsal root ganglia cultured in vitro were examined. All three local anesthetics show a sigmoidal dose-response relationship in inhibiting neurite outgrowth in a reversible fashion. The inhibition of growth is independent of the concentration of nerve growth factor and the in vitro culturing conditions. Morphological studies of cells treated with these anesthetics show that low dosages of the drugs (2.25 X10–3M lidocaine, 2 x 10–3M procaine, 1 x 10–4M tetracaine) cause a retraction of the microspikes into the growth cone and the formation of large swellings along the neurite and at the terminus. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) of these regions show that the loss of micro-spikes is concomitant with the loss of the bundles of microfilaments and much of the microfilament network. The large swellings are filled with an extensive array of smooth endoplasmic reticulum and agranular vesicles of various sizes. The microtubules and neurofilaments within the neurite fiber appear unaffected. Treatment with high dosages (5.0 x 10–3M lidocaine, 5.0 x 10–3M procaine, 5 x 10–4M tetracaine) results in a rapid wilting of the microspikes followed by retraction of the neurite. The inhibition of neurite outgrowth and the morphological changes induced by local anesthetics on nerves in culture are similar but not identical to those caused by cytochalasin B, colchicine, and the calcium ionophore A23187.