The de novo heterozygous p.L811P (c.2432T>C) gain-of-function mutation in the voltage-gated sodium (NaV) channel subtype 1.9 (gene name SCN11a) leads to congenital insensitivity to pain phenotype. Aside from sensorial distortions not associated with skin conditions or inflammation, which also includes severe pruritus, patients frequently report gastrointestinal (GI) distortions and discomfort that culminates in multiple hospital admissions for parenteral nutrition administration. However, different than pain or itch, the role of Nav1.9 in GI function is unexplored. Preliminary data have shown that the colon transit time is decreased in knockout mice, so I intend to further investigate the Nav1.9 role in the gut under normal and pathological conditions. In addition, since i) the enteric nervous system (ENS) communicates with central nervous system through autonomic pathways, ii) the Nav1.9 p.L811P patients also report dysautonomia symptoms and iii) our pilot experiments have revealed that NaV1.9 is present in the autonomic nervous system (ANS), I will evaluate the functionality of Nav1.9 is the ANS, where it may contribute to mutation-related GI pathology. In a broader context, my work will provide new conceptual insights into the role of Nav1.9 in the ANS-ENS, specially related to the gut (dys)function. This work has the potential to expand treatment methods for bowel disorders by pharmacologically manipulating NaV channels.