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 alpha-subunit have been detected in DRG neurons and transcripts encoding all three beta-subunits are also present. Interestingly, one alpha subunit, Na(v)1.8, is selectively expressed in C-fibre and Adelta fibre associated sensory neurons that are predominantly involved in damage sensing. Another channel, Na(v).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.

A peripheral nervous system actin-binding protein regulates neurite outgrowth.

Difference cloning has identified a Villin-like mRNA transcript expressed selectively in peripheral sensory and sympathetic neurons. Pervin, the encoded 820-amino acid protein, has 60% identity with Villin and is the rat homologue of Advillin. Coimmunoprecipitation studies demonstrate that Pervin and actin interact in vivo. Transfection of COS-7 epithelial cell lines demonstrates colocalization of epitope-tagged Pervin with green fluorescent protein-actin and results in an increase in process formation. This effect is abolished when the putative actin-bundling headpiece of Pervin is deleted. Biolistic transfection of primary cultures of rat dorsal root ganglion sensory neurons also results in increased neurite outgrowth with FLAG-tagged Pervin. Deletion of the actin-bundling headpiece inhibits normal neurite growth. These data suggest that Pervin may play a significant role in regulating process outgrowth in peripheral neurons through a mechanism that involves the activity of an actin-bundling domain.