Tetrodotoxin-resistant action potentials in dorsal root ganglion neurons are blocked by local anesthetics

Evidence from animal models and studies of human sensory nerves demonstrate that tetrodotoxin (TTX)-resistant Na+ channels are present in sensory neurons and might play an important role in pain conduction and chronic pain. Recent investigations suggest that TTX-resistant Na+ channels in the peripheral nervous system are less sensitive to local anesthetics than TTX-sensitive Na+ channels. To test the effects of the clinically used local anesthetics lidocaine and bupivacaine on TTX-resistant action potentials (APs) in sensory neurons, we performed electrophysiological experiments on small dorsal root ganglion (DRG) neurons from young rats. Amplitudes, time to peak and duration of TTX-resistant APs were measured in A delta- and C-type neurons using the patch-clamp technique in a thin slice preparation (150 I-Lm), thus avoiding enzymatic treatment. With increasing concentrations of the local anesthetics, the AP amplitude was gradually reduced but the AP did not disappear abruptly. The concentrations needed to reduce the amplitudes of TTX-resistant APs by half were 760 muM for lidocaine and 110 muM for bupivacaine. Time to peak and duration of TTX-resistant APs were prolonged by local anesthetics. Trains of APs could be elicited in some neurons by long-lasting current injections, and the half-maximal concentrations needed to suppress these trains were 30 muM tidocaine or 10 muM bupivacaine. We suggest that the reduction in firing frequency at low concentrations of local anesthetic may explain the phenomenon of poresthesia when sensory information is gradually suppressed during spinal anesthesia. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.