Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted NaV1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of NaV1.7 and/or NaV1.3. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.