Voltage-gated sodium channels (VGSC) are the primary mediators of electrical signal amplification and propagation in excitable cells. VGSC subtypes are diverse, with different biophysical and pharmacological properties, and varied tissue distribution. Altered VGSC expression and/or increased VGSC activity in sensory neurons is characteristic of inflammatory and neuropathic pain states. Therefore, VGSC modulators could be used in prospective analgesic compounds. VGSCs have specific binding sites for four conotoxin families: μ-, μO-, δ- and ί-conotoxins. Various studies have identified that the binding site of these peptide toxins is restricted to well-defined areas or domains. To date, only the μ- and μO-family exhibit analgesic properties in animal pain models. This review will focus on conotoxins from the μ- and μO-families that act on neuronal VGSCs. Examples of how these conotoxins target various pharmacologically important neuronal ion channels, as well as potential problems with the development of drugs from conotoxins, will be discussed.

Loss-of-function mutations in the pore-forming α subunit of the voltage-gated sodium channel 1.7 (Nav1.7) cause congenital indifference to pain and anosmia. We used immunohistochemical techniques to study Nav1.7 localization in the rat olfactory system in order to better understand its role in olfaction. We confirm that Nav1.7 is expressed on olfactory sensory axons and report its presence on vomeronasal axons, indicating an important role for Nav1.7 in transmission of pheromonal cues. Following neuroepithelial injury, Nav1.7 was transiently expressed by cells of monocytic lineage. These findings support an emerging role for Nav1.7 in immune function. This sodium channel may provide an important pharmacological target for treatment of inflammatory injury and inflammatory pain syndromes.