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Reduction of skin innervation is associated with a severe fibromyalgia phenotype

Dimitar Evdokimov, Johanna Frank, Alexander Klitsch, Stefan Unterecker, Bodo Warrings, Jordi Serra, Aikaterini Papagianni, Nadine Saffer, Caren Meyer Zu Altenschildesche, Daniel Kampik, Rayaz A Malik, Claudia Sommer, Nurcan Üçeyler
Annals of Neurology 2019 August 3

OBJECTIVES: To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS).

METHODS: 117 women with FMS underwent neurological examination, questionnaire assessment, neurophysiology, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P), and healthy women.

RESULTS: Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63% of FMS patients (MD-P: 10%, controls: 18%, p<0.001 each). We found four patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p<0.01 each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p<0.01), impaired C-tactile afferents (p<0.05), and reduced amplitudes (p<0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p<0.05 each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p<0.01) and length (p<0.05).

INTERPRETATION: The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS. This article is protected by copyright. All rights reserved.


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