['All local anesthetics (LAs) are, to some extent, neurotoxic. Toxicity studies have been performed in dissociated neuron cultures, immersing both axon and soma in LA. This approach, however, does not accurately reflect the in vivo situation for peripheral nerve blockade, where LA is applied to the axon alone.', 'We investigated lidocaine neurotoxicity in compartmental sensory neuron cultures, which are composed of one central compartment containing neuronal cell bodies and a peripheral compartment containing their axons, allowing for selective incubation. We applied lidocaine +/- neuroprotective drugs to neuronal somata or axons, and assessed neuron survival and axonal outgrowth.', 'Lidocaine applied to the peripheral compartment led to a decreased number of axons (to 59% +/- 9%), without affecting survival of cell bodies. During axonal incubation with lidocaine, the p38 mitogen-activated protein kinase inhibitor SB203580 (10 microM) attenuated axonal injury when applied to the axon (insignificant reduction of maximal axonal distance to 93% +/- 9%), but not when applied to the cell body (deterioration of maximal axonal length to 48% +/- 6%). Axonal co-incubation of lidocaine with the caspase inhibitor z-vad-fmk (20 microM) was not protective.'] Is in vitro , lidocaine-induced axonal injury prevented by peripheral inhibition of the p38 mitogen-activated protein kinase , but not by inhibiting caspase activity?