BLOCKADE OF NA-ANESTHETICS IN THE DORSAL HORN NEURONS OF THE SPINAL-CORD( AND K+ CURRENTS BY LOCAL)

Background: The dorsal horn of the spinal cord is a pivotal point for transmission of neuronal pain. During spinal and epidural anaesthesia, the neurons of the dorsal horn are exposed to local anesthetics, Unfo rtunately, little is known about the action of local anesthetics on th e major ionic conductances in dorsal horn neurons, In this article, th e authors describe the effects of bupivacaine, lidocaine, and mepivaca ine on voltage-gated Na+ and K+ currents in the membranes of these neu rons. Methods: The patch-clamp, technique was applied tee intact dorsa l horn neurons from laminae I-III identified in 200-mu m slices of spi nal cord from newborn rats, Under voltage-clamp conditions, the whole- cell Na+ and K+ currents activated by depolarization were recorded in the presence of different concentrations of local anesthetics, Results : Externally applied bupivacaine, lidocaine, and mepivacaine produced tonic block of Na+ currents with different potencies, Half-maximum inh ibiting concentrations (IC50) were 26, 112, and 324 mu M, respectively . All local anesthetics investigated also showed a phasic, that is, a use-dependent, block of Na+ channels, Rapidly inactivating K+ currents (K-A currents) also were sensitive to the blockers with IC50 values f or tonic blocks of 109, 163, and 236 mu M, respectively, The block of K-A currents was not use dependent. In contrast to Na+ and K-A current s, delayed-rectifier K+ currents were almost insensitive to the local anesthetics applied. Conclusions: In clinically relevant concentration s, local anesthetics block Na+ and K-A currents but not delayed-rectif ier K+ currents in spinal dorsal horn neurons. The molecular mechanism s of Na+ and K+ channel block by local anesthetics seem to be differen t. Characterization of these mechanisms could be are important step in understanding the complexity of local anesthetic action during spinal and epidural anesthesia.