Defining the Functional Role of Na_V1.7 in Human Nociception.

ABSTRACT: Loss-of-function mutations in Na_V1.7 cause congenital insensitivity to pain (CIP); this voltage-gated sodium channel is therefore a key target for analgesic drug development. Utilizing a multi-modal approach, we investigated how Na_V1.7 mutations lead to human pain insensitivity. Skin biopsy and microneurography revealed an absence of C-fiber nociceptors in CIP patients, reflected in a reduced cortical response to capsaicin on fMRI. Epitope tagging of endogenous Na_V1.7 revealed the channel to be localized at the soma membrane, axon, axon terminals, and the nodes of Ranvier of induced pluripotent stem cell (iPSC) nociceptors. CIP patient-derived iPSC nociceptors exhibited an inability to properly respond to depolarizing stimuli, demonstrating that Na_V

SUBMITTER: McDermott LA 

PROVIDER: S-EPMC6424805 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature