Sodium channels in primary sensory neurons: Relationship to pain states

Electrophysiological studies of dorsal root ganglion (DRG) neurons, and the results of PCR, Northern blot and in situ hybridization analyses have demonstrated the molecular diversity of Na⁺ channels that operate in sensory neurons. Several subtypes of α-subunit have been detected in DRG neurons and transcripts encoding all three β-subunits are also present. Interestingly, one α subunit, Na_v1.8, is selectively expressed in C-fibre and Aδ fibre associated sensory neurons that are predominantly involved in damage sensing. Another channel, Na_v1.3, is selectively up regulated in a variety of models of neuropathic pain. In this review we focus on Na⁺ channels that are selectively expressed in DRG neurons as potential analgesic drug targets. In the absence of subtype specific inhibitors, the production of null mutant mice provides useful information on the specialized functions of particular Na⁺ channels. A refinement of this approach is to delete Na⁺ channel genes flanked by lox-P sites in the sensory ganglia of adult animals, using viruses to deliver the bacteriophage Cre recombinase enzyme.