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.
Axon diameters of small dermal nerve fibers were reduced in patients with fibromyalgia compared with controls and patients with small fiber neuropathy.
aDepartment of Neurology, University Hospital Würzburg, Würzburg, Germany
bDepartment of Anesthesia and Critical Care, Interdisciplinary Pain Clinic, University Hospital Würzburg, Würzburg, Germany
cSchmerzklinik am Arkauwald, Bad Mergentheim, Germany
Corresponding author. Address: Department of Neurology, University Hospital Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. Tel.: +004993120123787; fax: +004993120123697. E-mail address: Doppler_K@ukw.de (K. Doppler).
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Received April 13, 2015
Received in revised form June 23, 2015
Accepted June 25, 2015