Sporadic onset of erythermalgia: A gain‐of‐function mutation in Na_v1.7

Abstract

Founder mutations in Na(v)1.7, which can confer hyperexcitability on peripheral sensory neurons, can underlie sporadic erythermalgia.

Gain-of-function mutation of a voltage-gated sodium channel NaV1.7 associated with peripheral pain and impaired limb development

“…This suggests that she acquired the mutation late in embryogenesis and that she is carrying it in a small number of cells as an adult. Mosaic individuals carrying other Na V 1.7 mutations have recalled burning pain as a youth and describe markedly improved symptoms as adults (29,31), which suggests the presence of the mutation in a smaller number sensory neurons, compared with their affected children. The role of sodium channels in limb development in humans is not fully understood.…”

Sodium Channel Nav1.7 Is Essential for Lowering Heat Pain Threshold after Burn Injury

“…Thus, single amino acid substitutions demonstrated to alter the biophysical gating properties of Na v 1.7 channels and to render DRG neurons hyperexcitable in culture manifest in these patients as a recurrent and debilitating pain syndrome triggered by exposure to warmth and usually described as "burning" (Cummins et al, 2004;DibHajj et al, 2005DibHajj et al, , 2008Han et al, 2006Han et al, , 2009Harty et al, 2006;Rush et al, 2006;Estacion et al, 2008;Lampert et al, 2008;Choi et al, 2010;Cheng et al, 2011). Whether Na v 1.7 contributes similarly to pain following burn injury has thus far remained unexplored.…”

Inherited Pain

“…To our knowledge, this is the first description of a mosaic for a heterozygous SCN9A missense mutation that causes a clinical phenotype. A single case of mosaicism (heterozygous p.L858F) in SCN9A linked to IEM has been described, but the individual was clinically asymptomatic (20). It may be possible that differences in the degree or distri- bution of the mosaicism may play a role.…”