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Updated: Apr 30, 2026

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies
Published on: April 29, 2013
Intraepidermal nerve fiber density of healthy human
Objectives:
To analyze intraepidermal nerve fiber density (IEFND) by skin biopsy, evaluate the effect of age, anatomical sites, and ethnic origin on IEFND and develop a reference range of IENFD at the distal leg of healthy human.
Methods:
Seventy skin biopsy specimens from surgical procedures involving 70 patients were analyzed. Specimens were fixed routinely in formalin and thereafter embedded in paraffin. Nerve fibers of 10-μm-thick sections were observed using immunoperoxidase staining with panaxonal antibody protein gene product 9·5 (PGP 9·5). The morphology of intraepidermal nerve fibers (IENFs) and the IENFD was determined using light microscope. The statistical analysis was performed with SPSS 16·0 software.
Results:
No significant correlation was observed between IENFD and age (Pwrist = 0·830, Pdistal leg = 0·478). The significant correlation was observed between IENFD and anatomic site (P = 0·001), the IENFD of upper arm and proximal thigh were significantly higher than that of wrist and distal leg. The reference range for IENFD of distal leg in normal Chinese humans was 40·55 fibers/mm(2). The IEFND of Chinese healthy human was significantly lower than that of Finnish (62·87 ± 15·25 vs 114·617 ± 32·322 fibers/mm(2), P < 0·05).
Discussion:
Skin biopsy may be a useful tool in sensory neuropathies. IENFD is independent of age, but varies in different parts of the body. The proximal sites have a higher IENFD, but no significant difference is found between the wrist and distal leg.
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