BACKGROUND: The addition of epinephrine to local anesthetics has been known to prolong the duration of neural blokade and to increase the intensity of analgesia, but underlying mechanisms are unclear. This study was designed to investigate electrophysiologically the analgesic effects of epinephrine and its interaction with tetracaine. METHODS: Whole cell patch clamp recordings were made from acutely dissociated neurons from adult rat dorsal root ganglion (DRG). Using voltage clamp method, we compared the IC50 values of tetracaine for Na+ and Ca2+ channel suppression in the absence and presence of a fixed dose of epinephrine. Action potentials evoked by current pulses were also investigated to evaluate the effect of tetracaine and epinephrine on the excitability of DRG neurons. RESULTS: Clinical doses of epinephrine did not alter the dose-response curves of tetracaine for peak Na+ and Ca2+ channel current, but the amplitude of action potential spikes was reduced and firing rates evoked by sustained current pulse increased. The addition of epinephrine did not affect the changes of action potential parameters caused by tetracaine alone. CONCLUSIONS: The ability of epinephrine to increase the intensity of analgesia induced by tetracaine seems more likely due to an analgesic action at the level of spinal cord rather than a direct analgesic action at a level of primary sensory neurons. Local vasoconstriction and stimulation of descending inhibitory system via alpha-adrenergic pathway may play a role.