DOWN-REGULATION OF TETRODOTOXIN-RESISTANT SODIUM CURRENTS AND UP-REGULATION OF A RAPIDLY REPRIMING TETRODOTOXIN-SENSITIVE SODIUM CURRENT INSMALL SPINAL SENSORY NEURONS AFTER NERVE INJURY

Clinical and experimental studies have shown that spinal sensory neuro ns become hyperexcitable after axonal injury, and electrophysiological changes have suggested that this may be attributable to changes in so dium current expression. We have demonstrated previously that sodium c hannel alpha-III mRNA levels are elevated and sodium channel alpha-SNS mRNA levels are reduced in rat spinal sensory neurons after axotomy. In this study we show that small (C-type) rat spinal sensory neurons e xpress sodium currents with dramatically different kinetics after axot omy produced by sciatic nerve ligation, Uninjured C-type neurons expre ss both slowly inactivating tetrodotoxin-resistant (TTX-R) sodium curr ent and a fast-inactivating tetrodotoxin-sensitive (TTX-S) current tha t reprimes (recovers from inactivation) slowly, After axotomy, the TTX -R current density was greatly reduced, No difference was observed in the density of TTX-S currents after axotomy, and their voltage depende nce was not different from controls. However, TTX-S currents in axotom ized neurons reprimed four times faster than control TTX-S currents. T hese data indicate that axotomy of spinal neurons is followed by downr egulation of TTX-R current and by the emergence of a rapidly repriming TTX-S current and suggest that this may be attributable to the upregu lation of a sodium channel isoform that was unexpressed previously in these cells, These axotomy-induced changes in sodium currents are expe cted to alter excitability substantially and could underlie the molecu lar pathogenesis of some chronic pain syndromes associated with injury to the axons of spinal sensory neurons.