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Increased cutaneous miR-let-7d expression correlates with small nerve fiber pathology in patients with fibromyalgia syndrome

Leinders, Mathias; Doppler, Kathrin; Klein, Thomas; Deckart, Maximiliane; Rittner, Heike; Sommer, Claudia; Üçeyler, Nurcan

doi: 10.1097/j.pain.0000000000000668
Research Paper

Fibromyalgia syndrome (FMS) is a chronic widespread pain condition probably comprising subgroups with different underlying pathomechanisms. There is increasing evidence for small nerve fiber impairment in subgroups of patients with FMS. MicroRNAs (miRNAs) regulate molecular factors determining nerve de- and re-generation. We investigated whether systemic and cutaneous miRNA expression in patients with FMS is related to small nerve fiber pathology. We confirmed previous findings of disturbed small fiber function and reduced intraepidermal nerve fiber density in subgroups of patients with FMS. We found 51 aberrantly expressed miRNAs in white blood cells of patients with FMS, of which miR-let-7d correlated with reduced small nerve fiber density in patients with FMS. Furthermore, we demonstrated miR-let-7d and its downstream target insulin-like growth factor-1 receptor as being aberrantly expressed in skin of patients with FMS with small nerve fiber impairment. Our study gives further evidence of small nerve fiber pathology in FMS subgroups and provides a missing link in the pathomechanism that may lead to small fiber loss in subgroups of patients with FMS.

Supplemental Digital Content is Available in the Text.Small fiber pathology is present in subgroups of patients with fibromyalgia syndrome. We provide first evidence for cutaneous microRNA dysregulation as one potential mechanism.

aDepartment of Neurology, University of Würzburg, Würzburg, Germany

bPain Clinic Am Arkauwald, Bad Mergentheim, Germany

cDepartment of Anesthesiology, University of Würzburg, Würzburg, Germany

Corresponding author. Address: Department of Neurology, University of Würzburg, Josef-Schneider-Straße 11, Würzburg 97080, Germany. Tel.: 0931-201-23542; fax: 0931-201-623542. E-mail address: (N. Üçeyler).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received May 21, 2016

Received in revised form June 24, 2016

Accepted July 08, 2016

© 2016 International Association for the Study of Pain
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