Small-fiber neuropathy: Expanding the clinical pain universe

Maurice Sopacua, Janneke G.J. Hoeijmakers, Ingemar S.J. Merkies, Giuseppe Lauria, Stephen G. Waxman, Catharina G. Faber

Research output: Contribution to journalArticle


Small-fiber neuropathy (SFN) is a disorder of thinly myelinated Aδ 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 Nav1.7, Nav1.8 and Nav1.9 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
JournalJournal of the Peripheral Nervous System
Publication statusAccepted/In press - Jan 1 2019


  • diagnostic criteria
  • neuropathic pain
  • pain management
  • small-fiber neuropathy
  • sodium channel variants

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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  • Cite this

    Sopacua, M., Hoeijmakers, J. G. J., Merkies, I. S. J., Lauria, G., Waxman, S. G., & Faber, C. G. (Accepted/In press). Small-fiber neuropathy: Expanding the clinical pain universe. Journal of the Peripheral Nervous System.