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Small fibre pathology in patients with fibromyalgia syndrome

Nurcan Üçeyler, Daniel Zeller, Ann-Kathrin Kahn, Susanne Kewenig, Sarah Kittel-Schneider, Annina Schmid, Jordi Casanova-Molla, Karlheinz Reiners, Claudia Sommer
DOI: http://dx.doi.org/10.1093/brain/awt053 First published online: 9 March 2013

Summary

Fibromyalgia syndrome is a clinically well-characterized chronic pain condition of high socio-economic impact. Although the pathophysiology is still unclear, there is increasing evidence for nervous system dysfunction in patients with fibromyalgia syndrome. In this case-control study we investigated function and morphology of small nerve fibres in 25 patients with fibromyalgia syndrome. Patients underwent comprehensive neurological and neurophysiological assessment. We examined small fibre function by quantitative sensory testing and pain-related evoked potentials, and quantified intraepidermal nerve fibre density and regenerating intraepidermal nerve fibres in skin punch biopsies of the lower leg and upper thigh. The results were compared with data from 10 patients with monopolar depression without pain and with healthy control subjects matched for age and gender. Neurological and standard neurophysiological examination was normal in all patients, excluding large fibre polyneuropathy. Patients with fibromyalgia syndrome had increased scores in neuropathic pain questionnaires compared with patients with depression and with control subjects (P < 0.001 each). Compared with control subjects, patients with fibromyalgia syndrome but not patients with depression had impaired small fibre function with increased cold and warm detection thresholds in quantitative sensory testing (P < 0.001). Investigation of pain-related evoked potentials revealed increased N1 latencies upon stimulation at the feet (P < 0.001) and reduced amplitudes of pain-related evoked potentials upon stimulation of face, hands and feet (P < 0.001) in patients with fibromyalgia syndrome compared to patients with depression and to control subjects, indicating abnormalities of small fibres or their central afferents. In skin biopsies total (P < 0.001) and regenerating intraepidermal nerve fibres (P < 0.01) at the lower leg and upper thigh were reduced in patients with fibromyalgia syndrome compared with control subjects. Accordingly, a reduction in dermal unmyelinated nerve fibre bundles was found in skin samples of patients with fibromyalgia syndrome compared with patients with depression and with healthy control subjects, whereas myelinated nerve fibres were spared. All three methods used support the concept of impaired small fibre function in patients with fibromyalgia syndrome, pointing towards a neuropathic nature of pain in fibromyalgia syndrome.

  • fibromyalgia syndrome
  • small fibre neuropathy
  • skin biopsy
  • quantitative sensory testing
  • pain related evoked potentials
  • Abbreviations
    ADS
    ‘Allgemeine Depressionsskala’, i.d. German version of the Centre for Epidemiologic Studies Depression Scale
    IENFD
    intraepidermal nerve fibre density
    NPSI-G
    German version of the Neuropathic Pain Symptom Inventory
    PREP
    pain-related evoked potential
    QST
    quantitative sensory testing
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