The aim of the present study was to investigate the action of liwdocaine and tramadol on the abnormal impulse characteristics of injured peripheral nerves. The ultrastructure of nerves was studied with electron microscopy and the action of lidocaine and tramadol on intact and injured rat sciatic nerves was examined by using the sucrose gap recording technique. Tramadol and lidocaine caused concentration- and frequency-dependent decreases in the amplitude of the compound action potential. Injured nerves were more sensitive to lidocaine than to tramadol. Lidocaine suppressed the delayed depolarization and decreased the hyperpolarizing after potentials to a greater extent than did tramadol. A low concentration of lidocaine may restore the abnormal impulse characteristics of injured nerves without changing the normal impulse pattern. The efficacy of lidocaine and inefficacy of tramadol on abnormal impulse characteristics may contribute, at least in part, to our understanding of the mechanisms of action of these drugs in neuropathic pain therapy. (c) 2006 Elsevier B.V. All rights reserved.