@article{9d6260bb2ec84c0689780e642ad65af5,
title = "Somatotopic heat pain thresholds and intraepidermal nerve fibers in health",
abstract = "Introduction: For sequential and somatotopic assessment of small fiber neuropathy, heat pain (HP) tests of hypoalgesia might be used instead of decreased counts of epidermal nerve fibers (ENFs), but then healthy subject reference values of HP thresholds are needed. Methods: Using the Computer Assisted Sensation Evaluator IVc system, HP thresholds of hypoalgesia were estimated for 10 unilateral sites and counts of ENFs for 4 of them in healthy subjects. Results: In healthy subjects, small but statistically significant differences of both HP thresholds of hypoalgesia and counts of ENFs were observed among tested sites. Significant correlations between HP thresholds and counts of ENFs were not found. Discussion: For the studied somatotopic sites, we provide ≥95th and ≥99th percentile reference limits for HP 0.5 and 5 of 1–10 HP thresholds of hypoalgesia and decreased counts of ENFs at ≤5th and ≤1st percentile levels. Muscle Nerve 58: 509–516, 2018.",
keywords = "distal polyneuropathy, epidermal nerve fibers, heat pain tests of hypoalgesia, heat pain thresholds, small fiber neuropathy, somatotopic sites",
author = "Davies, {Jenny L.} and Engelstad, {Janean K.} and {E. Gove}, Linde and Linbo, {Linda K.} and Carter, {Rickey E.} and Christopher Lynch and Staff, {Nathan P.} and Klein, {Christopher J.} and Dyck, {P. James B.} and Herrmann, {David N.} and Dyck, {Peter J.}",
note = "Funding Information: The age and gender of healthy subjects at different somatotopic sites are shown in Table. For HP tests, limb sites were more frequently studied than face or trunk sites as described in Materials and Methods. For ENF counts, an even lower number of healthy subjects were evaluated. For most somatotopic sites, HP thresholds had been assessed broadly from ages ≥18 years to old age and for both men and women (Fig.). Plotted HP5 threshold values and regression lines of healthy subjects at 3 lower limb and an abdominal site. Note that threshold regression lines increase with age and this increase is statistically significant for leg and foot. Not shown are threshold values for 6 other somatotopic sites. The regression lines for HP5 threshold on age were remarkably similar among the 10 somatotopic sites studied. All regression lines increased with advancing age. This increase was statistically significant at lateral leg and foot sites for the 50th percentile line (Fig.). The regression lines of counts of ENF on age were similar among the tested anatomic sites, although intermediate ages had not been tested for the thigh and leg sites. For all tested sites, there was a decrease in counts of epidermal nerve fibers with age and this was statistically significant for the 50th percentile line for the thigh and leg sites (Fig.). Plotted values and regression lines of counted epidermal nerve fiber densities with age. For these sites, regression lines show a decrease with age, and this was statistically significant for thigh and leg sites. In Table, we compare the 50th, 95th, and 99th percentile regression line y intercepts at age 18 years for HP5 (of 1–10 pain severity) at the 10 studied somatotopic sites and ENF 50th, 5th, and 1st y intercepts at 3 lower limb and 1 abdominal site. Whereas ENF density regression line intercepts increase from most distal (foot) to most proximal (lower abdomen) sites, this was not the case for HP5 thresholds. Likelihood ratios and t-tests were used to assess HP5 and ENF regression line differences among somatotopic sites (Tables and). Statistically significant differences were found, but the magnitude of these differences were small. Whereas ENF densities decreased progressively from lower abdomen to anterior thigh, lateral leg, and dorsal foot, a monotone increase in HP5 thresholds from abdomen to foot was not observed. In a second analysis, we assessed for the correlation of HP thresholds (HP0.5 or HP5) with counts of ENFs at each of the 4 assessed somatotopic sites using Spearman's Rank Correlation. Of the 8 analyses, none showed a significant correlation (Supplementary Table S1). Funding Information: Abbreviations: A1c, glycated hemoglobin; CASE IVc, Computer Assisted Sensation Evaluator IVc; DPN, distal polyneuropathy; ENFs, epidermal nerve fibers; HP, heat pain; HP0.5, heat pain threshold 0.5 of 1–10 severity; HP5, heat pain stimulus response 5 of 1–10 severity; HP5-0.5, heat pain stimulus response slope; PGP 9.5, protein gene product; QSTs, quantitative sensation tests. Key words: distal polyneuropathy; epidermal nerve fibers; heat pain tests of hypoalgesia; heat pain thresholds; small fiber neuropathy; somatotopic sites Funding: The authors have received previous financial support from NS14304 and NS36797 for the recruitment and study of healthy subjects. Peter J. Dyck, Jenny Davies, and Linde Gove have received financial support from Ionis, Inc., Carlsbad, California and Alnylam, Inc., Cambridge, Massachusetts for training of investigators in the conduct of oligonucleotide therapeutic trials in transthyretin amyloid polyneuropathy. Nathan P. Staff receives support from NCI CA169433. David N. Herrmann receives grant support through NIH U54 NS065712-08, the Muscular Dystrophy Association, and has received compensation for scientific consulting activities from Acceleron, Inc., Flex Pharma, Inc., Guidepoint Global, Gerson Lehrman Group, and LAM Therapeutics/ and honoraria from Medpace for activities related to safety monitoring for a therapeutic trial in transthyretin amyloid polyneuropathy Publisher Copyright: {\textcopyright} 2018 Wiley Periodicals, Inc.",
year = "2018",
month = oct,
doi = "10.1002/mus.26128",
language = "English (US)",
volume = "58",
pages = "509--516",
journal = "Muscle and Nerve",
issn = "0148-639X",
publisher = "John Wiley and Sons Inc.",
number = "4",
}