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.
Competing Interests: Declarations. Conflict of interest: Anne Marshall, Mohamed Elshafei, Frank G Preston, Jamie Burgess, Nicola Goodson, Nicholas Fallon, Bernhard Frank, Sizheng Steven Zhao declare no relevant conflicts of interest. Uazman Alam has no relevant conflicts of interests pertaining to this manuscript but  declares that he has received honoraria from Viatris, Grünenthal, Eli Lilly, Procter & Gamble for educational meetings and has received investigator-led funding form Proctor & Gamble. Uazman Alam has also received sponsorship to attend educational meetings from Daiichi Sankyo and Sanofi. Ethical approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.
(© 2025. The Author(s).)