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Reduction of skin innervation is associated with a severe fibromyalgia phenotype
Author(s) -
Evdokimov Dimitar,
Frank Johanna,
Klitsch Alexander,
Unterecker Stefan,
Warrings Bodo,
Serra Jordi,
Papagianni Aikaterini,
Saffer Nadine,
Meyer zu Altenschildesche Caren,
Kampik Daniel,
Malik Rayaz A.,
Sommer Claudia,
Üçeyler Nurcan
Publication year - 2019
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25565
Subject(s) - microneurography , medicine , skin biopsy , nerve fiber , fibromyalgia , nociception , sensory nerve , anesthesia , sensory system , biopsy , anatomy , neuroscience , psychology , baroreflex , heart rate , receptor , blood pressure
Objective To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS). Methods One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, 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 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced ( p < 0.01 for 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 for 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. ANN NEUROL 2019;86:504–516