Small-fiber neuropathy: Expanding the clinical pain universe

M. Sopacua, J.G.J. Hoeijmakers, I.S.J. Merkies, G. Lauria, S.G. Waxman, C.G. Faber*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

34 Citations (Web of Science)
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Abstract

Small-fiber neuropathy (SFN) is a disorder of thinly myelinated A delta and unmyelinated C fibers. SFN is clinically dominated by neuropathic pain and autonomic complaints, leading to a significant reduction in quality of life. According to international criteria, the diagnosis is established by the assessment of intraepidermal nerve fiber density and/or quantitative sensory testing. SFN is mainly associated with autoimmune diseases, sodium channel gene variants, diabetes mellitus, and vitamin B12 deficiencies, although in more than one half of patients no etiology can be identified. Recently, gain-of-function variants in the genes encoding for the Na(v)1.7, Na(v)1.8 and Na(v)1.9 sodium channel subunits have been discovered in SFN patients, enlarging the spectrum of underlying conditions. Sodium channel gene variants associated with SFN can lead to a diversity of phenotypes, including different pain distributions and presence or absence of autonomic symptoms. This suggests that SFN is part of a clinical continuum. New assessments might contribute to a better understanding of the cellular and molecular substrates of SFN and might provide improved diagnostic methods and trial designs in the future. Identification of the underlying mechanisms may inform the development of drugs that more effectively address neuropathic pain and autonomic symptoms of SFN.
Original languageEnglish
Pages (from-to)19-33
Number of pages15
JournalJournal of the Peripheral Nervous System
Volume24
Issue number1
DOIs
Publication statusPublished - 1 Mar 2019

Keywords

  • amyotrophic-lateral-sclerosis
  • autosomal-dominant
  • congenital insensitivity
  • corneal confocal microscopy
  • diagnostic criteria
  • inherited erythromelalgia
  • laser-evoked potentials
  • na(v)1.7 sodium-channels
  • neuropathic pain
  • of-function mutation
  • pain management
  • scn9a mutations
  • skin biopsy
  • small-fiber neuropathy
  • sodium channel variants
  • SKIN BIOPSY
  • INHERITED ERYTHROMELALGIA
  • OF-FUNCTION MUTATION
  • NA(V)1.7 SODIUM-CHANNELS
  • CONGENITAL INSENSITIVITY
  • SCN9A MUTATIONS
  • AMYOTROPHIC-LATERAL-SCLEROSIS
  • LASER-EVOKED POTENTIALS
  • CORNEAL CONFOCAL MICROSCOPY
  • AUTOSOMAL-DOMINANT

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