Central and peripheral dimensions of fibromyalgia: a multivariate clinical profiling of migraine and small fibre pathology
Marina de Tommaso, Elena Ammendola, Livio Clemente, Giulia Paparella, Giuseppe Libro, Giulia PaparellaIntroduction:
Fibromyalgia is a heterogeneous chronic pain disorder involving both central and peripheral mechanisms. Migraine is considered a disorder with abnormal central multimodal and pain stimuli processing, whereas small fibre pathology (SFP) reflects peripheral nociceptive dysfunction. We investigated whether migraine and SFP identify distinct clinical profiles within the fibromyalgia spectrum.
Methods:
In this retrospective cross-sectional study, 296 patients with fibromyalgia underwent standardized clinical assessment and skin biopsy for intraepidermal nerve fibre density (IENFD). Migraine was classified as low-frequency episodic, high-frequency episodic, or chronic. Clinical severity was assessed in pain, disability, associated symptoms, and psychological domains. Multivariate analysis of covariance evaluated the independent and combined effects of migraine subtype and SFP. Subgroup analyses and correlation of clinical symptoms with IENFD were performed.
Results:
Migraine was diagnosed in 138 patients (46.6%; 69 low-frequency episodic, 28 high-frequency episodic, and 41 chronic migraine). Reduced IENFD was detected in 191 patients (64.5%), and its prevalence did not differ across migraine subtypes. The primary multivariate analysis of covariance did not demonstrate significant multivariate effects of migraine subtype, small fibre pathology, or their interaction. Exploratory subgroup analyses identified higher disability and associated symptom scores in patients with concomitant chronic migraine and small fibre pathology.
Conclusions:
Chronic migraine is associated with greater clinical burden in fibromyalgia, whereas small fibre pathology does not identify a distinct multidimensional clinical phenotype. Although patients with concomitant chronic migraine and small fibre pathology showed greater disability and associated symptom burden in exploratory analyses, these findings require confirmation in prospective studies.