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Updated: Jun 23, 2026

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies
Published on: April 29, 2013
Stimulated skin wrinkling for predicting intraepidermal nerve fibre density
Einar P Wilder-Smith1, Yaling Guo, Adeline Chow
1Division of Neurology, National University Singapore, 5 Lower Kent Ridge Road, Singapore 119074, Singapore. mdcwse@nus.edu.sg
Objective:
To determine the usefulness of stimulated skin wrinkling using EMLA and water immersion in detecting abnormal intraepidermal nerve fibre density.
Methods:
In a prospective study of patients with predominantly sensory polyneuropathy, we tested sensitivity and specificity of stimulated skin wrinkling using EMLA and water immersion in detecting abnormal intraepidermal nerve fibre density (IENFD).
Results:
EMLA stimulated wrinkling showed a sensitivity of 81.6% and specificity of 74.7% in detecting abnormal IENFD and water wrinkling a sensitivity of 71.4% and specificity of 73%. The positive and negative predictive values for detecting abnormal IENFD were 88.3% and 63.3% for EMLA wrinkling, for water wrinkling 83.3% and 57.4%. Intra-observer EMLA score variability was good with no change in assignment of wrinkling and inter-observer score variability resulted in 1-5 changes in wrinkling score which translated into a change of the wrinkling status from normal to abnormal on two occasions.
Conclusions:
Stimulated skin wrinkling correlates well with abnormal intraepidermal nerve fibre density.
Significance:
Our study suggests that EMLA induced stimulated skin wrinkling is a useful alternative parameter for predicting abnormal intraepidermal nerve fibre density.
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