Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous NaV channel gene, in particular a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous NaV channel gene, in particular a replacement of the endogenous NaV1.7 gene with a human NaV1.7 gene, and wherein the genetically modified non-human animals are capable of generating action potentials and communicating through the excitable cells of the genetically modified non-human animals via the expressed human or humanized NaV1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized NaV1.7 gene from the endogenous NaV1.7 locus, and wherein the mice comprise functional β-subunits.