title: Dermal innervation in healthy subjects and small fiber neuropathy patients: a stereological reappraisal.
abstract: The aim of this study was to estimate dermal nerve fiber length (DNFL) using a stereological sampling technique in comparison with a previously reported manual estimation. DNFL was analyzed in skin punch biopsy specimens from 24 healthy volunteers and 18 patients with small fiber neuropathy (SFN) using global spatial sampling that yields unbiased and reliable length estimation. The estimation was carried out in 50-µm biopsy sections after immunostaining with anti-protein gene product (PGP) 9.5 antibodies. The length of the PGP9.5-positive dermal nerves from the dermal-epidermal junction and 200 µm down was measured (DNFL mm(-2) ). Results were compared with our previously reported manual method. Patients showed a significantly (p < 0.0001) lower DNFL (105 mm(-2)  ± 6.4 SD) than healthy subjects (246 mm(-2)  ± 8.39 SD). Moderate correlation with age was observed for both healthy subjects (Pearson's r = -0.33) and patients (Pearson's r = -0.59). A significant (p < 0.001) correlation between global spatial sampling and manual estimation was observed in both patients and healthy subjects (Pearson's r = 0.62 and 0.61, respectively). These findings provide further evidence on the reliability of dermal nerve morphometry in human skin and strengthen the hypothesis that dermal nerve fibers undergo significant degeneration in SFN.
authors.affiliation: Danish Pain Research Center, Aarhus University Hospital, DK-8000 Aarhus C, Denmark. pall.karlsson@ki.au.dk
authors.forename: Páll
authors.initials: P
authors.lastname: Karlsson
authors.forename: Carla
authors.initials: C
authors.lastname: Porretta-Serapiglia
authors.forename: Raffaella
authors.initials: R
authors.lastname: Lombardi
authors.forename: Troels S
authors.initials: TS
authors.lastname: Jensen
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
mesh_terms: D000328:Adult; D000368:Aged; D020405:Dermis / Q000294:innervation* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology*; D009422:Nervous System Diseases / Q000473:pathology* / Q000503:physiopathology; D009431:Neural Conduction / Q000502:physiology; D015203:Reproducibility of Results; D013238:Stereotaxic Techniques; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase