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Abstract. Introduction:. Small fiber pathology may be involved in the pathophysiology of pain in women with fibromyalgia syndrome (FMS). Objectives:. This prospective single-center case-control study provides detailed pain phenotyping and small fiber pathology data in a cohort of men with FMS on a morphological and functional level. Methods:. Forty-two men with FMS underwent a comprehensive pain-related interview and neurological examination, a questionnaire and neurophysiological assessment, and specialized small fiber tests: skin punch biopsy, quantitative sensory testing including C-tactile afferents, and corneal confocal microscopy. Data were compared with those of healthy male controls. Results:. Men with FMS reported generalized and permanent pain with additional pain attacks and a mostly pressing pain character. Intraepidermal nerve fiber density was reduced at ≥1 biopsy site in 35 of 42 (83%) men with FMS (controls: 32/65, 49%). Compared with male controls, men with FMS had elevated cold (P < 0.05) and warm detection thresholds (P < 0.001) and an increased mechanical pain threshold (P < 0.05) as well as an impairment of C-tactile afferents (P < 0.05). Corneal nerve fiber density was lower in male patients with FMS vs healthy men (P < 0.01). Male FMS patients with pathological skin innervation at ≥1 biopsy site compared with those with normal skin innervation had a higher clinical Widespread Pain Index (P < 0.05) indicating an association between the severity of cutaneous denervation and symptom load. Conclusion:. We show a distinct pain phenotype and small nerve fiber dysfunction and pathology in male patients with FMS. These findings may have implications for the diagnosis and management of men with FMS.

ObjectivesThe pathogenesis of fibromyalgia syndrome (FMS) is unclear. Transcranial ultrasonography revealed anechoic alteration of midbrain raphe in depression and anxiety disorders, suggesting affection of the central serotonergic system. Here, we assessed midbrain raphe echogenicity in FMS.MethodsSixty-six patients underwent transcranial sonography, of whom 53 were patients with FMS (27 women, 26 men), 13 patients with major depression and physical pain (all women), and 14 healthy controls (11 women, 3 men). Raphe echogenicity was graded visually as normal or hypoechogenic, and quantified by digitized image analysis, each by investigators blinded to the clinical diagnosis.ResultsQuantitative midbrain raphe echogenicity was lower in patients with FMS compared to healthy controls (pConclusionWe found reduced echogenicity of the midbrain raphe area in patients with FMS and in patients with depression and physical pain, independent of the presence or severity of pain, FMS, and depressive symptoms. Further exploration of this sonographic finding is necessary before this objective technique may enter diagnostic algorithms in FMS and depression.