Myelinated nerve endings in human skin

Abstract

We used immunohistochemical techniques and confocal microscopy to study the morphometry of myelinated nerve endings in glabrous and hairy skin. A total of 30 healthy volunteers took part in this study designed to assess the possibility of obtaining reliable information on myelinated fibers using samples of hairy skin and to determine whether differences exist between myelinated terminations from different sites. We obtained consistent information on cutaneous myelinated terminations using hairy as well as glabrous skin samples. Myelinated endings from hairy and glabrous skin differ in density and distribution. However, from a comparison of our findings with data from nerve biopsy studies, we conclude that all cutaneous myelinated terminations are thinner terminal branches of large myelinated A beta fibers, whereas cutaneous terminations of small myelinated A delta fibers lose their myelin before entering the dermis and become indistinguishable from C-fiber terminations. The classic criteria, based on fiber size, used to distinguish myelinated fiber subgroups in sensory nerves are therefore not suitable for identifying myelinated terminations in the skin.

Small nerve fiber involvement in CMT1A

“…24 However, some of our findings (warm threshold abnormalities and ENF loss) also suggest an involvement of C fibers in CMT1A, although we cannot have morphologic evidence, since it is not possible to distinguish between C and A-d fibers, whose cutaneous terminal branches are both unmyelinated. 25,26 The involvement of small fibers in conditions affecting mainly large fibers has been previously reported, [27][28][29] implying that congenital or acquired mechanisms underlying the degeneration of large fibers may also affect small fibers. In CMT1A, abnormalities of the interaction between axon and Schwann cells may play a causative role in the distal degeneration of unmyelinated fibers, since PMP22 is also present in the plasma membrane of nonmyelinating Schwann cells.…”

Charcot-Marie-Tooth disease

“…Skin biopsies increasingly offer a minimally invasive approach to overcome this problem. Beginning with studies of glabrous 3 and hairy skin, 4 these biopsies have already provided pathogenic information in sensory nerves from patients with CMT1A, such as reduced Meissner corpuscles (MC) density, shortened internodal length, and abnormal paranodaljuxtaparanodal architecture. 5,6 In the present study, we extend these observations in a larger series of patients.…”

“…Nodal gap was measured as the length of the fiber not marked by MBP ( figure 1, B.a and B.b) and included nodal and part of paranodal regions. 3,4 The measurement of internodal length was performed only when 2 consecutive nodes were identified by tracing the internode on the Z-stack of confocal images (figure 1B.c). Four caliber measurements for each internode (figure 1B.d) were obtained and a mean value was reported.…”

New technologies for the assessment of neuropathies

“…In one study, analysis of the density of parts of the subepidermal nerve plexus with immunofluorescence -when associated with the quantification of IENF density -improved the sensitivity of skin biopsy for diagnosis of SFN 133 . In another study, internode length and internodal gap length of myelinated dermal nerve fibres were quantified and combined with the findings of nerve biopsy, and suggested that the fibres are thin endings of large myelinated Aβ fibres 134 . The same group used this approach to investigate patients with CMT, and demonstrated similar internodal shortening associated with different causal mutations, and a wider nodal gap in the CMT type 1A, providing insight into their role in determining changes of conduction velocity 135,136 .…”