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Nav1.7 mutations associated with paroxysmal extreme pain disorder, but not erythromelalgia, enhance Navβ4 peptide‐mediated resurgent sodium currents
Author(s) -
Theile Jonathan W.,
Jarecki Brian W.,
Piekarz Andrew D.,
Cummins Theodore R.
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.200915
Subject(s) - erythromelalgia , sodium channel , medicine , peripheral , pain disorder , nav1 , neuroscience , chronic pain , anesthesia , sodium , biology , chemistry , psychiatry , organic chemistry
Non‐technical summary Abnormal pain sensitivity associated with inherited and acquired pain disorders occurs through increased excitability of peripheral sensory neurons in part due to changes in the properties of voltage‐gated sodium channels (Navs). Resurgent sodium currents ( I NaR ) are atypical currents believed to be associated with increased excitability of neurons and may have implications in pain. Mutations in Nav1.7 (peripheral Nav isoform) associated with two genetic pain disorders, inherited erythromelalgia (IEM) and paroxysmal extreme pain disorder (PEPD), enhance Nav1.7 function via distinct mechanisms. We show that changes in Nav1.7 function due to mutations associated with PEPD, but not IEM, are important in I NaR generation, suggesting that I NaR may play a role in pain associated with PEPD. This knowledge provides us with a better understanding of the mechanism of I NaR generation and may lead to the development of specialized treatment for pain disorders associated with I NaR .