Increased excitability of primary sensory neurons may be important for the generation of neuropathic pain from nerve injury. The currents underlying the action potentials of these neurons are largely carried by Na+, and changes in Na+ currents have been postulated to contribute to this increased excitability. Using patch clamp in whole-cell mode, we recorded Na+ currents from DRG neurons freshly isolated from rats with a chronic constriction injury (CCI), an animal model of neuropathic pain. We found significant changes in Na+ currents after CCI when cell size and Na+ channel properties were used to segregate DRG neurons. Most changes were concentrated in small neurons (< or = 25 microm diameter) and in the slow TTX-resistant current that is predominant in these cells. CCI produced two principal changes in these cells: it shifted the voltage-dependence of activation of the TTX-resistant current to more negative potentials and it reduced the average density of this current. The decrease in density appears to be primarily due to the decrease in the number of small neurons expressing this current. The net result is a change in both activation and steady-state inactivation properties of the total Na+ current to more negative potentials without a significant change in the density of total Na+ current. The change in activation properties of the TTX-resistant Na+ current are similar to those produced by some hyperalgesic autacoids, and may contribute to the increase in primary afferent excitability and hyperalgesia that occurs after this lesion.