The effect of age and gender on epidermal nerve fiber density
Abstract
OBJECTIVE: Sensory neuropathies often involve small-diameter myelinated and unmyelinated nerve fibers, and neurologic and electrophysiologic findings may be normal unless larger nerve fibers are involved. The small (intra)epidermal nerve fibers (ENFs) now can be visualized with immunohistochemical techniques using the panaxonal marker anti-protein gene product 9.5 (PGP 9.5). Using this technique, the authors have established a reference range for ENF in a healthy white population and evaluated the reliability of the method. METHODS: Two punch biopsies, 3 mm in diameter, were taken from the distal part of the leg in 106 healthy volunteers (mean age, 49.0 +/- 19.6 years). Fifty-micrometer frozen thick sections were incubated with rabbit polyclonal antibodies to human PGP 9.5. The number of ENF/mm then was reported as the mean of counts in six sections (three sections from each of the two biopsies). RESULTS: The mean number of ENFs was 12.4 +/- 4.6 mm. In a multiple regression model, the density of ENF depended on age and gender (Y = 13.92 + 2.25 (gender) - 0.06 x age). The mean difference in ENF by intraobserver analysis was 0.2 +/- 1.2 ENF/mm, and by interobserver analysis, it was 0.4 +/- 1.5 fibers/mm. CONCLUSION: Normal means and ranges for the density of epidermal nerve fibers in a reference population have been established. The density of epidermal nerve fibers decreases with age and is lower in men compared with women. Intraobserver and interobserver analysis proves the r…
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Several healthy men in the control cohort had a reduced IENFD, as shown in previous studies, although all participants were screened negative for known causes of small fiber pathology.
“Furthermore, several healthy men in our control cohort had a reduced IENFD as already shown in previous studies13,19 although all participants were screened negative for known causes of small fiber pathology.”
From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [19]
The authors' normative values for IENFD are based merely on one standard deviation from the mean, and published studies reported similar or higher cut-off values.
“Our normative values for IENFD are already based merely on one standard deviation from the mean, considering that published studies addressing normative values for IENFD reported similar or even higher cut-off values.19,24,29”
From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [19]
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References 18 · Cited by 207
- Authors
- Gøransson, L. G., Mellgren, S. I., Lindal, S., & Omdal, R.
- Affiliations
- University Hospital of North Norway (NO)
- Venue
- Neurology
- Published
- 2004-03-09
- Volume
- 62
- Issue
- 5
- Pages
- 774-777
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2087340224
- Cited by
- 207
- References
- 18
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 9 · 2023: 4 · 2022: 13 · 2021: 4 · 2020: 6 · 2019: 12 · 2018: 9 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 13 · 2013: 11 · 2012: 11
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Keywords
- epidermal nerve fibers, intraepidermal nerve fibers, PGP 9.5, sensory neuropathy, age effects, sex differences, reference values, skin biopsy, method reliability, small nerve fibers
- MeSH terms
- Adult, Aged, Aging, Epidermis, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Fibers, Reference Values, Reproducibility of Results, Ubiquitin Thiolesterase, White People
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