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Review
. 2025 Apr;14(2):461-478.
doi: 10.1007/s40122-024-00696-1. Epub 2025 Jan 13.

Small Fibre Pathology in Fibromyalgia: A review

Anne Marshall #  1 , Mohamed Elshafei #  1 , Frank G Preston  1   2 , Jamie Burgess  1 , Nicola Goodson  2   3 , Nicholas Fallon  4 , Bernhard Frank  1   5 , Sizheng Steven Zhao  6 , Uazman Alam  7   8
Affiliations
Review

Small Fibre Pathology in Fibromyalgia: A review

Anne Marshall et al. Pain Ther. 2025 Apr.

Abstract

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.

Keywords: Corneal confocal microscopy; Fibromyalgia syndrome; Quantitative sensory testing; Skin biopsy; Small fibre pathology; Small nerve fibre.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Examples of skin biopsy images from healthy individuals (top) and people with fibromyalgia syndrome (FMS) (bottom); note reduction in the number of intraepidermal nerve fibres in the images from individuals with FMS (bottom). Original images
Fig. 2
Fig. 2
Examples of CCM images from healthy individuals (A, B) and people with SFP and FMS (C–F); note reduction in the number of corneal nerves and number of branching nerves in the images from individuals with SFP and FMS (C–F). Original images
See this image and copyright information in PMC

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