While small-fiber pathology is common in patients with fibromyalgia, it has no significant effect on the somatosensory system function and most likely has no major role in the symptoms of the disease, according to study results published in Pain.

Previous studies have shown that small-fiber neuropathy — including abnormal C-fiber activity or reduced intra-epidermal nerve fiber density — is common in patients with fibromyalgia; however, no data exist on the role of small-fiber neuropathy in the clinical features of the disease. The objective of the current study was to determine whether small-fiber pathology has any clinically important effect on the somatosensory system function.

The study sample included 57 patients (54 women; mean age 45.9±9.9 years) with fibromyalgia, including 18 patients with evidence of small-fiber pathology with a reduction in intraepidermal nerve fiber density at the distal leg skin biopsy and 39 patients without small-fiber pathology.

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All participants completed clinical and diagnostic tests, including questionnaires, a nerve conduction study, quantitative sensory testing (QST), and laser-evoked potentials to assess somatosensory system function. In addition, voltage-gated sodium channel genotyping was completed.

In most patients with small-fiber pathology, QST and laser-evoked potential variables were in the normal range. There were no differences in clinical measures, QST, and laser-evoked potential variables between patients with and without small-fiber pathology. Although there were no clinically important somatosensory system abnormalities, autonomic symptoms were common in both groups, with no difference between patients with and without small-fiber pathology.

Beck Depression Inventory II score compatible with depression (≥14) was reported in half (n=9) of all patients with small-fiber neuropathy and in 24 patients without small-fiber neuropathy. High catastrophizing tendency (≥29), measured by the Pain Catastrophizing Scale, was documented in half of all patients with small-fiber neuropathy and in 17 patients without small fiber neuropathy. Pain severity was not different between patients with and without small-fiber pathology, suggesting reduction in intraepidermal nerve fiber density had no impact on fibromyalgia severity.

Genetic analysis showed that 2 patients with small-fiber pathology and 1 patient without small fiber pathology had rare variants of voltage-gated sodium channels, including SCN11A, SCN9A, and SCN1A variants. Gain of function mutations in Nav1.9, encoded by SCN11A, were previously reported in patients with small fiber neuropathy. These findings suggest that small fiber neuropathy due to voltage-gated sodium channel mutation may be misdiagnosed with fibromyalgia.

The study had several limitations, including the exploratory research design and the relatively small sample size.

“These findings therefore suggest that small-fiber pathology in patients with fibromyalgia does not significantly affect somatosensory system function and probably does not play a noteworthy role in the fibromyalgia symptoms,” concluded the researchers.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Fasolino A, Di Stefano G, Leone C, et al. Small-fibre pathology has no impact on somatosensory system function in patients with fibromyalgia. Pain. 2020;161(10):2385-2393. doi: 10.1097/j.pain.0000000000001920.