Sodium channels and neuropathic pain.

Although it has long been known that sodium channels play an important role in the generation of abnormal neuronal activity and neuropathic pain, it is only recently that we have begun to understand the subtypes of sodium channels which are particularly important in neuropathic pain. Many of the identified subtypes of sodium channels are localized in dorsal root ganglion (DRG) neurons. Based on their sensitivity to tetrodotoxin (TTX), these sodium channels are classified as TTX-sensitive (TTXs) or TTX-resistant (TTXr) subtypes. In in vitro electrophysiological experiments, ectopic discharges arising from DRG neurons with injured axons are blocked by TTX at doses that are too low to block TTXr subtypes. Furthermore, the same low doses of TTX applied to the DRG of the injured segment in neuropathic rats significantly reduce pain behaviours. These data suggest that TTXs subtypes of sodium channels are playing an important role in the generation of both ectopic discharges and neuropathic pain. Analysis of mRNA of the TTXs subtypes of sodium channels in the DRG after spinal nerve ligation showed that Nav1.3 (Type III) and Nax (NaG) are the only two subtypes that are up-regulated, suggesting their potentially important role in ectopic discharge and neuropathic pain generation.