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Cited by 312Fibromyalgia and Chronic Fatigue Syndrome ResearchPeripheral Neuropathies and DisordersPain Mechanisms and Treatments

Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia

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Oaklander, Anne Louise, Herzog, Zeva Daniela, Downs, Heather M., Klein, Max M.·2013·Pain
DOI 10.1016/j.pain.2013.06.001PMC PMC3845002
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Abstract

Fibromyalgia is a common, disabling syndrome that includes chronic widespread pain plus diverse additional symptoms. No specific objective abnormalities have been identified, which precludes definitive testing, disease-modifying treatments, and identification of causes. In contrast, small-fiber polyneuropathy (SFPN), despite causing similar symptoms, is definitionally a disease caused by the dysfunction and degeneration of peripheral small-fiber neurons. SFPN has established causes, some diagnosable and definitively treatable, eg, diabetes. To evaluate the hypothesis that some patients labeled as having fibromyalgia have unrecognized SFPN that is causing their illness symptoms, we analyzed SFPN-associated symptoms, neurological examinations, and pathological and physiological markers in 27 patients with fibromyalgia and in 30 matched normal controls. Patients with fibromyalgia had to satisfy the 2010 American College of Rheumatology criteria plus present evidence of a physician's actual diagnosis of fibromyalgia. The study's instruments comprised the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), distal-leg neurodiagnostic skin biopsies, plus autonomic-function testing (AFT). We found that 41% of skin biopsies from subjects with fibromyalgia vs 3% of biopsies from control subjects were diagnostic for SFPN, and MNSI and UENS scores were higher in patients with fibromyalgia than in control subjects (all P ≤ 0.001). Abnormal AFTs were equally prevalent, suggesting that fibromyalgia-associated SFPN is primarily somatic. Blood tests from subjects with fibromyalgia and SFPN-diagnostic skin biopsies provided insights into causes. All glucose tolerance tests were normal, but 8 subjects had dysimmune markers, 2 had hepatitis C serologies, and 1 family had apparent genetic causality. These findings suggest that some patients with chronic pain labeled as fibromyalgia have unrecognized SFPN, a distinct disease that can be tested for objectively and sometimes treated definitively.

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  • Peripheral nervous system involvement in a subgroup of women with fibromyalgia syndrome provided a new perspective.

    “peripheral nervous system involvement in a subgroup of women with FMS provided a new perspective32,41,50”

    From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [32]

  • The exact impact of the peripheral nervous system on pain in fibromyalgia syndrome is still a matter of debate.

    “however, the exact impact of the peripheral nervous system on pain in FMS is still a matter of debate.”

    From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [32]

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Authors
Oaklander, A. L., Herzog, Z. D., Downs, H. M., & Klein, M. M.
Affiliations
Harvard University (US)
Corresponding author
Oaklander, Anne Louise
ORCID
Venue
Pain
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-11
Volume
154
Issue
11
Pages
2310-2316
ISSN
0304-3959 (ISSN-L)
DOI
10.1016/j.pain.2013.06.001
PMC
PMC3845002
OpenAlex
W1976288643
Cited by
312
References
5
Citations by year
2026: 16 · 2025: 17 · 2024: 15 · 2023: 11 · 2022: 27 · 2021: 29 · 2020: 26 · 2019: 26 · 2018: 19 · 2017: 27 · 2016: 31 · 2015: 37 · 2014: 22 · 2013: 6 · 2012: 1
FWCI
22.75
Type
journal article
Language
en
Open access
Locations
  • Pain (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
Funders
  • National Institute of Neurological Disorders and Stroke (R01NS093653, K24NS059892)
  • National Center for Research Resources (UL1RR025758, UIL RR025758)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords
small fiber polyneuropathy, fibromyalgia, chronic widespread pain, skin biopsy, Michigan Neuropathy Screening Instrument, autonomic dysfunction, hepatitis C, genetic causality, misdiagnosis
MeSH terms
Adolescent, Adult, Aged, Data Interpretation, Statistical, Female, Fibromyalgia, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Fibers, Pain Measurement, Polyneuropathies, Surveys and Questionnaires, Skin, Reproducibility of Results, Treatment Outcome, Sample Size, Young Adult

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