Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting of sensory neurons

SD Dib-Hajj, AM Rush, TR Cummins, FM Hisama… - Brain, 2005 - academic.oup.com
SD Dib-Hajj, AM Rush, TR Cummins, FM Hisama, S Novella, L Tyrrell, L Marshall…
Brain, 2005academic.oup.com
Erythromelalgia is an autosomal dominant disorder characterized by burning pain in
response to warm stimuli or moderate exercise. We describe a novel mutation in a family
with erythromelalgia in SCN9A, the gene that encodes the Nav1. 7 sodium channel. Nav1. 7
produces threshold currents and is selectively expressed within sensory neurons including
nociceptors. We demonstrate that this mutation, which produces a hyperpolarizing shift in
activation and a depolarizing shift in steady-state inactivation, lowers thresholds for single …
Abstract
Erythromelalgia is an autosomal dominant disorder characterized by burning pain in response to warm stimuli or moderate exercise. We describe a novel mutation in a family with erythromelalgia in SCN9A, the gene that encodes the Nav1.7 sodium channel. Nav1.7 produces threshold currents and is selectively expressed within sensory neurons including nociceptors. We demonstrate that this mutation, which produces a hyperpolarizing shift in activation and a depolarizing shift in steady-state inactivation, lowers thresholds for single action potentials and high frequency firing in dorsal root ganglion neurons. Erythromelalgia is the first inherited pain disorder in which it is possible to link a mutation with an abnormality in ion channel function and with altered firing of pain signalling neurons.
Oxford University Press