Small fiber neuropathy in women with fibromyalgia. An in vivo assessment using corneal confocal bio-microscopy
Abstract
Objective A consistent line of investigation suggests that fibromyalgia is a neuropathic pain syndrome. This outlook has been recently reinforced by several controlled studies that describe decreased small nerve fiber density in skin biopsies of patients with fibromyalgia. The cornea receives the densest small fiber innervation of the body. Corneal confocal bio-microscopy is a new noninvasive method to evaluate small nerve fiber morphology. Our objective was to assess corneal small nerve fiber morphology in patients with fibromyalgia, and to associate corneal nerve microscopic features with neuropathic pain descriptors and other fibromyalgia symptoms. Methods We studied 17 female patients with fibromyalgia and 17 age-matched healthy control subjects. All the participants completed different questionnaires regarding the symptoms of fibromyalgia, including a neuropathic pain survey. A central corneal thickness scan was obtained with a confocal microscope. Nerve measurements were made by a single ophthalmologist without knowledge of the clinical diagnosis. Stromal nerve thickness was defined as the mean value between the widest and the narrowest portion of each analyzed stromal nerve. Corneal sub-basal plexus nerve density was also assessed. Results Patients with fibromyalgia had stromal nerve thickness of 5.0 ± 1.0 µm (mean ± standard deviation) significantly different from that of control's values (6.1 ± 1.3) p = 0.01. Patients also had decreased sub-basal plexus nerve density per square millimeter (85 ± 29) vs. 107 ± 26 of controls p = 0.02. When controls and patients were grouped together, there was an association between stromal nerve slenderness and neuropathic pain descriptors (Fisher's exact test p = 0.007). Conclusion Women suffering from fibromyalgia have thinner corneal stromal nerves and diminished sub-basal plexus nerve density when compared to healthy controls. Nerve scarcity is associated with neuropathic pain descriptors. Small fiber neuropathy may play a role in the pathogenesis of fibromyalgia pain. Corneal confocal microscopy could become a useful test in the study of patients with fibromyalgia.
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Another CCM study in women with FMS reported no correlation between corneal nerve fiber parameters and FMS-specific questionnaire results.
“Another CCM study in women with FMS also reported no correlation between corneal nerve fiber parameters and the results of FMS-specific questionnaires.36”
From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [36]
Cites
Wolfe, F., Clauw, D. J., Fitzcharles, M., Goldenberg, D. L., Katz, R. S., Mease, P., Russell, A. S., Russell, I. J., Winfield, J. B., & Yunus, M. B. (2010) · Arthritis Care & Research · doi:10.1002/acr.20140 · Cited by 3,952 · see citing works
Fibromyalgia: A Clinical Review
Clauw, D. J. (2014) · JAMA · doi:10.1001/jama.2014.3266 · Cited by 1,674 · see citing works
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Reduction of skin innervation is associated with a severe fibromyalgia phenotype
Evdokimov, D., Frank, J., Klitsch, A., Unterecker, S., Warrings, B., Serra, J., Papagianni, A., Saffer, N., Meyer zu Altenschildesche, C., Kampik, D., et al. (2019) · Annals of Neurology · doi:10.1002/ana.25565 · Cited by 152 · see citing works
Central Sensitization and Small-fiber Neuropathy Are Associated in Patients With Fibromyalgia
Dumolard, A., Lefaucheur, J.-P., Hodaj, E., Liateni, Z., Payen, J.-F., & Hodaj, H. (2023) · The Clinical Journal of Pain · doi:10.1097/ajp.0000000000001085 · Cited by 26 · see citing works
Pain and small fiber pathology in men with fibromyalgia syndrome
Feulner, B., Gross, F., Evdokimov, D., Malik, R. A., Kampik, D., & Üçeyler, N. (2024) · PAIN Reports · doi:10.1097/pr9.0000000000001212 · Cited by 8 · see citing works
- Authors
- Ramírez, M., Martínez-Martínez, L.-A., Hernández-Quintela, E., Velazco-Casapía, J., Vargas, A., & Martínez-Lavín, M.
- Affiliations
- Asociacion Para Evitar la Ceguera en México Hospital Dr. Luis Sánchez Bulnes (MX)
- Instituto Nacional de Cardiología (MX)
- Venue
- Seminars in Arthritis and Rheumatism
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 45
- Issue
- 2
- Pages
- 214-219
- ISSN
- 0049-0172 (ISSN-L)
- OpenAlex
- W1993891730
- Cited by
- 108
- References
- 2
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 5 · 2023: 12 · 2022: 9 · 2021: 7 · 2020: 13 · 2019: 14 · 2018: 11 · 2017: 13 · 2016: 9 · 2015: 3
- FWCI
- 9.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Seminars in Arthritis and Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Keywords
- fibromyalgia, small fiber neuropathy, corneal confocal microscopy, corneal nerve fiber density, neuropathic pain, women
- MeSH terms
- Adult, Cornea, Erythromelalgia, Female, Fibromyalgia, Humans, Middle Aged, Pain Measurement, Severity of Illness Index, Microscopy, Confocal
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