title: Pathological nociceptors in two patients with erythromelalgia-like symptoms and rare genetic Nav 1.9 variants.
abstract: The sodium channel Nav 1.9 is expressed in peripheral nociceptors and has recently been linked to human pain conditions, but the exact role of Nav 1.9 for human nociceptor excitability is still unclear.
  
  
  
  C-nociceptors from two patients with late onset of erythromelalgia-like pain, signs of small fiber neuropathy, and rare genetic variants of Nav 1.9 (N1169S, I1293V) were assessed by microneurography.
  
  
  
  Compared with patients with comparable pain phenotypes (erythromelalgia-like pain without Nav-mutations and painful polyneuropathy), there was a tendency toward more activity-dependent slowing of conduction velocity in mechanoinsensitive C-nociceptors. Hyperexcitability to heating and electrical stimulation were seen in some nociceptors, and other unspecific signs of increased excitability, including spontaneous activity and mechanical sensitization, were also observed.
  
  
  
  Although the functional roles of these genetic variants are still unknown, the microneurography findings may be compatible with increased C-nociceptor excitability based on increased Nav 1.9 function.
authors: Section of Clinical Neurophysiology Department of Neurology Oslo University Hospital-Rikshospitalet Oslo Norway.
authors: Inge P
authors: IP
authors: Kleggetveit
authors: Department of Clinical Neurophysiology Uppsala University Uppsala Sweden.
authors: Roland
authors: R
authors: Schmidt
authors: Institute of Physiology and Pathophysiology Friedrich-Alexander-Universität Erlangen-Nürnberg Erlangen Germany.
authors: Barbara
authors: B
authors: Namer
authors: AstraZeneca Translational Science Centre Department of Clinical Neuroscience Karolinska Institutet Solna Sweden.
authors: Hugh
authors: H
authors: Salter
authors: Section of Clinical Neurophysiology Department of Neurology Oslo University Hospital-Rikshospitalet Oslo Norway.
authors: Tormod
authors: T
authors: Helås
authors: Department of Anesthesiology Mannheim Heidelberg University Mannheim Germany.
authors: Martin
authors: M
authors: Schmelz
authors: Section of Clinical Neurophysiology Department of Neurology Oslo University Hospital-Rikshospitalet Oslo Norway.
authors: Ellen
authors: E
authors: Jørum
mesh_terms: D004916:Erythromelalgia / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D062558:NAV1.9 Voltage-Gated Sodium Channel / Q000235:genetics; D009619:Nociceptors / Q000473:pathology
chemical_list: D062558:NAV1.9 Voltage-Gated Sodium Channel; C491886:SCN11A protein, human
keywords: microneurography; nociceptors; pain