Reduced dermal nerve fiber diameter in skin biopsies of patients with fibromyalgia

Pain. 2015 Nov;156(11):2319-2325. doi: 10.1097/j.pain.0000000000000285.


Recent studies have provided evidence of pathology and functional abnormalities of small nerve fibers as a potential correlate of pain in the fibromyalgia syndrome. Here, we aimed to quantify dermal unmyelinated nerve fiber diameter at the electron microscopic level to find a potential morphological correlate of the functional disturbance. Thirty-two patients with fibromyalgia syndrome, 12 patients with small fiber neuropathy, and 24 healthy controls were prospectively recruited. Skin biopsies of the distal and proximal legs and index finger were taken and processed for immunofluorescence and for electron microscopy. We determined the diameter of small unmyelinated nerve fibers by measuring ten transversely cut axons of each biopsy. The mean axon diameter was reduced in patients with fibromyalgia syndrome compared with patients with small fiber neuropathy and controls (P < 0.05). Furthermore, we confirmed previous findings of disturbed small fiber function in quantitative sensory testing and of reduced intraepidermal nerve fiber density in patients with fibromyalgia. Our study provides further evidence of small fiber pathology in fibromyalgia syndrome and discloses differences compared with small fiber neuropathy, indicating that different pathomechanisms may lead to small fiber loss in the 2 disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Electric Stimulation
  • Female
  • Fibromyalgia / pathology*
  • Humans
  • Male
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Nerve Fibers, Unmyelinated / metabolism
  • Nerve Fibers, Unmyelinated / pathology*
  • Nerve Fibers, Unmyelinated / physiology
  • Nerve Fibers, Unmyelinated / ultrastructure
  • Neural Conduction / physiology
  • Pain Measurement
  • Schwann Cells / pathology
  • Schwann Cells / ultrastructure
  • Skin / innervation*
  • Skin / ultrastructure
  • Statistics, Nonparametric
  • Ubiquitin Thiolesterase / metabolism


  • UCHL1 protein, human
  • Ubiquitin Thiolesterase