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 Adelta- and C-type neurons using the patch-clamp technique in a thin slice preparation (150 microm), 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 microM for
lidocaine and 110 microM 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 microM
lidocaine or 10 microM
bupivacaine. We suggest that the reduction in firing frequency at low concentrations of
local anesthetic may explain the phenomenon of
paresthesia when sensory information is gradually suppressed during
spinal anesthesia.