Alteration of Na+ currents in dorsal root ganglion neurons from rats with a painful neuropathy

Increased excitability of primary sensory neurons may be important for the generation of neuropathic pain from nerve injury. The currents underlying t he action potentials of these neurons are largely carried by Na+, and chang es in Na+ currents have been postulated to contribute to this increased exc itability. Using patch clamp in whole-cell mode, we recorded Na+ currents f rom DRG neurons freshly isolated from rats with a chronic constriction inju ry (CCT), an animal model of neuropathic pain. We found significant changes in Na+ currents after CCI when cell size and Na+ channel properties were u sed to segregate DRG neurons. Most changes were concentrated in small neuro ns (less than or equal to 25 mu m diameter) and in the slow TTX-resistant c urrent that is predominant in these cells. CCI produced two principal chang es in these cells: it shifted the voltage-dependence of activation of the T TX-resistant current to more negative potentials and it reduced the average density of this current. The decrease in density appears to be primarily d ue 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 activ ation properties of the TTX-resistant Na+ current are similar to those prod uced by some hyperalgesic autacoids, and may contribute to the increase in primary afferent excitability and hyperalgesia that occurs after this lesio n. (C) 1999 International Association for the Study of Pain. Published by E lsevier Science B.V.