Small Fibre Pathology in Fibromyalgia: A review

Fibromyalgia syndrome (FMS) presents a complex and challenging disorder in both the diagnosis and treatment, with emerging evidence suggesting a role of small fibre pathology (SFP) in its pathophysiology. The significance of the role of SFP in FMS remains unclear; however, recent evidence suggests degeneration and dysfunction of the peripheral nervous system, particularly small unmyelinated fibres, which may influence pathophysiology and underlying phenotype. Both skin biopsy and corneal confocal microscopy (CCM) have consistently demonstrated that ~ 50% of people with FMS have SFP. CCM, a non-invasive measure of small nerve fibres has detected small fibre loss, correlating with neuropathic pain descriptors. Additionally, quantitative sensory testing has shown abnormalities, primarily in pain pressure/mechanical pain thresholds. This narrative review provides a comprehensive understanding of the pathophysiological dimensions of FMS with a clear focus on small nerve fibres and the peripheral nervous system, offering a roadmap for future research.