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Innervation of the Human Skin: From the Structure and Function to the Pathology

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Dermatology".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 26200

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Special Issue Editor

Prof. Dr. José A. Vega

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Guest Editor

1. Grupo SINPOS, Departamento de Morfología y Biología Celular, Universidad de Oviedo, Avda, Julián Clavería, 6. 33006 Oviedo, Spain
2. Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile
Interests: peripheral nervous system; primary sensory neurons; dorsal root ganglia; mechanoreceptors; cutaneous end-organ complexes (sensory corpuscles)
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Special Issue Information

Dear Colleagues,

Human skin is supplied by somatosensory and autonomic nerves. The former ending in the dermis forming different morphotypes of sensory corpuscles, and free nerve endings (dermal and epidermal), or contacting specialized epithelial cells, like Merkel cells. The sensory corpuscles and the Merkel cell-neurite complexes are involved in the detection of different forms of mechanosensation. Free nerve endings are particularly related to nociception. In recent years, the molecular mechanisms of the functioning of these sensory formations have been clarified, and recently it has been reported that not only the axons but also the glial cells that form them could participate in touch detection. As for the autonomic nerves, they are in relation to the efferent innervation of the glands and blood vessels of the skin, participating in processes such as sweating or control of vascular pressure. Both somatosensory nerve fibers and sensitive corpuscles, as well as autonomic fibers, are altered in some systemic metabolic diseases, neurodegenerative diseases, specific diseases of the nerves, as well as tumors as in the case of Merkel cells.

This Special Issue of Journal of Clinical Medicine aims to update all those aspects related to the skin nervous system.

Prof. Dr. José A. Vega
Guest Editor

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Keywords

sensory nerves
autonomic nerves
sensory corpuscles
Merkel cells
pain
itch
tumors

Published Papers (5 papers)

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Research

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15 pages, 2285 KiB

Open AccessArticle

Involvement of Cutaneous Sensory Corpuscles in Non-Painful and Painful Diabetic Neuropathy

by Yolanda García-Mesa, Jorge Feito, Mario González-Gay, Irene Martínez, Jorge García-Piqueras, José Martín-Cruces, Eliseo Viña, Teresa Cobo and Olivia García-Suárez

J. Clin. Med. 2021, 10(19), 4609; https://doi.org/10.3390/jcm10194609 - 08 Oct 2021

Cited by 12 | Viewed by 2681

Abstract

Distal diabetic sensorimotor polyneuropathy (DDSP) is the most prevalent form of diabetic neuropathy, and some of the patients develop gradual pain. Specialized sensory structures present in the skin encode different modalities of somatosensitivity such as temperature, touch, and pain. The cutaneous sensory structures responsible for the qualities of mechanosensitivity (fine touch, vibration) are collectively known as cutaneous mechanoreceptors (Meissner corpuscles, Pacinian corpuscles, and Merkel cell–axonal complexes), which results are altered during diabetes. Here, we used immunohistochemistry to analyze the density, localization within the dermis, arrangement of corpuscular components (axons and Schwann-like cells), and expression of putative mechanoproteins (PIEZO2, ASIC2, and TRPV4) in cutaneous mechanoreceptors of subjects suffering clinically diagnosed non-painful and painful distal diabetic sensorimotor polyneuropathy. The number of Meissner corpuscles, Pacinian corpuscles, and Merkel cells was found to be severely decreased in the non-painful presentation of the disease, and almost disappeared in the painful presentation. Furthermore, there was a marked reduction in the expression of axonal and Schwann-like cell markers (with are characteristics of corpuscular denervation) as well as of all investigated mechanoproteins in the non-painful distal diabetic sensorimotor polyneuropathy, and these were absent in the painful form. Taken together, these alterations might explain, at least partly, the impairment of mechanosensitivity system associated with distal diabetic sensorimotor polyneuropathy. Furthermore, our results support that an increasing severity of DDSP may increase the risk of developing painful neuropathic symptoms. However, why the absence of cutaneous mechanoreceptors is associated with pain remains to be elucidated. Full article

(This article belongs to the Special Issue Innervation of the Human Skin: From the Structure and Function to the Pathology)

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12 pages, 4180 KiB

Open AccessArticle

Vibration Perception Thresholds of Skin Mechanoreceptors Are Influenced by Different Contact Forces

by Claudio Zippenfennig, Bert Wynands and Thomas L. Milani

J. Clin. Med. 2021, 10(14), 3083; https://doi.org/10.3390/jcm10143083 - 13 Jul 2021

Cited by 15 | Viewed by 2863

Abstract

Determining vibration perception thresholds (VPT) is a central concern of clinical research and science to assess the somatosensory capacity of humans. The response of different mechanoreceptors to an increasing contact force has rarely been studied. We hypothesize that increasing contact force leads to a decrease in VPTs of fast-adapting mechanoreceptors in the sole of the human foot. VPTs of 10 healthy subjects were measured at 30 Hz and 200 Hz at the heel of the right foot using a vibration exciter. Contact forces were adjusted precisely between 0.3 N–9.6 N through an integrated force sensor. Significant main effects were found for frequency and contact force. Furthermore, there was a significant interaction for frequency and contact force, meaning that the influence of an increasing contact force was more obvious for the 30 Hz condition. We presume that the principles of contrast enhancement and spatial summation are valid in Meissner and Pacinian corpuscles, respectively. In addition to spatial summation, we presume an effect on Pacinian corpuscles due to their presence in the periosteum or interosseous membrane. Full article

(This article belongs to the Special Issue Innervation of the Human Skin: From the Structure and Function to the Pathology)

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13 pages, 2114 KiB

Open AccessArticle

Low and High Frequency Vibration Perception Thresholds Can Improve the Diagnosis of Diabetic Neuropathy

by Tina J. Drechsel, Renan L. Monteiro, Claudio Zippenfennig, Jane S. S. P. Ferreira, Thomas L. Milani and Isabel C. N. Sacco

J. Clin. Med. 2021, 10(14), 3073; https://doi.org/10.3390/jcm10143073 - 12 Jul 2021

Cited by 9 | Viewed by 2258

Abstract

Recent studies demonstrate neuropathic changes with respect to vibration sensitivity for different measurement frequencies. This study investigates the relationship between vibration perception thresholds (VPTs) at low and high frequencies at two plantar locations and diabetic peripheral neuropathy (DPN) severity in diabetes mellitus (DM) subjects with DPN. We examine differences of VPTs between participants with DM, with DPN, as well as healthy controls. The influence of anthropometric, demographic parameters, and DM duration on VPTs is studied. Thirty-three healthy control group subjects (CG: 56.3 ± 9.9 years) and 33 with DM are studied. DM participants are subdivided into DM group (DM without DPN, n = 20, 53.3 ± 15.1 years), and DPN group (DM with DPN, n = 13, 61.0 ± 14.5 years). VPTs are measured at the first metatarsal head (MTH1) and heel (30 Hz, 200 Hz), using a customized vibration exciter. Spearman and Pearson correlations are used to identify relationships between VPTs and clinical parameters. ANOVAs are calculated to compare VPTs among groups. Significant correlations are observed between DPN severity (by fuzzy scores) and VPTs at both locations and frequencies (MTH1_30 Hz vs. fuzzy: r = 0.68, p = 0.011; Heel_30 Hz vs. fuzzy: r = 0.66, p = 0.014; MTH1_200 Hz vs. fuzzy: r = 0.73, p = 0.005; Heel_200 Hz vs. fuzzy: r = 0.60, p = 0.032). VPTs in CG and DM groups are significantly smaller than the DPN group, showing higher contrasts for the 30 Hz compared to the 200 Hz measurement. The correlations between fuzzy scores and VPTs confirm the relevance of using low and high frequencies to assess a comprehensive foot sensitivity status in people with DM. Full article

(This article belongs to the Special Issue Innervation of the Human Skin: From the Structure and Function to the Pathology)

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11 pages, 1857 KiB

Open AccessArticle

The Mechanoreceptor’s Role in Plantar Skin Changes in Individuals with Diabetes Mellitus

by Claudio Zippenfennig, Tina J. Drechsel, Renan L. Monteiro, Isabel C. N. Sacco and Thomas L. Milani

J. Clin. Med. 2021, 10(12), 2537; https://doi.org/10.3390/jcm10122537 - 08 Jun 2021

Cited by 11 | Viewed by 2315

Abstract

Mechanical skin properties (MSPs) and vibration perception thresholds (VPTs) show no relationship in healthy subjects. Similar results were expected when comparing MSP and VPT in individuals with diabetes mellitus (DM) and with diabetic (peripheral-)neuropathy (DPN). A healthy control group (33 CG), 20 DM and 13 DPN participated in this cross-sectional study. DM and DPN were classified by using a fuzzy decision support system. VPTs (in µm) were measured with a modified vibration exciter at two different frequencies (30 and 200 Hz) and locations (heel, first metatarsal head). Skin hardness (durometer readings) and thickness (ultrasound) were measured at the same locations. DPN showed the highest VPTs compared to DM and CG at both frequencies and locations. Skin was harder in DPN compared to CG (heel). No differences were observed in skin thickness. VPTs at 30 and 200 Hz correlated negatively with skin hardness for DPN and with skin thickness for DM, respectively. This means, the harder or thicker the skin, the better the perception of 30 or 200 Hz vibrations. Changes in MSP may compensate the loss of sensitivity up to a certain progression of the disease. However, the influence seems rather small when considering other parameters, such as age. Full article

(This article belongs to the Special Issue Innervation of the Human Skin: From the Structure and Function to the Pathology)

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Review

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12 pages, 4885 KiB

Open AccessReview

The Human Cutaneous Sensory Corpuscles: An Update

by Ramón Cobo, Jorge García-Piqueras, Juan Cobo and José A. Vega

J. Clin. Med. 2021, 10(2), 227; https://doi.org/10.3390/jcm10020227 - 10 Jan 2021

Cited by 49 | Viewed by 13267

Abstract

Sensory corpuscles of human skin are terminals of primary mechanoreceptive neurons associated with non-neuronal cells that function as low-threshold mechanoreceptors. Structurally, they consist of an extreme tip of a mechanosensory axon and nonmyelinating peripheral glial cells variably arranged according to the morphotype of the sensory corpuscle, all covered for connective cells of endoneurial and/or perineurial origin. Although the pathologies of sensitive corpuscles are scarce and almost never severe, adequate knowledge of the structure and immunohistochemical profile of these formations is essential for dermatologists and pathologists. In fact, since sensory corpuscles and nerves share a basic structure and protein composition, a cutaneous biopsy may be a complementary method for the analysis of nerve involvement in peripheral neuropathies, systemic diseases, and several pathologies of the central nervous system. Thus, a biopsy of cutaneous sensory corpuscles can provide information for the diagnosis, evolution, and effectiveness of treatments of some pathologies in which they are involved. Here, we updated and summarized the current knowledge about the immunohistochemistry of human sensory corpuscles with the aim to provide information to dermatologists and skin pathologists. Full article

(This article belongs to the Special Issue Innervation of the Human Skin: From the Structure and Function to the Pathology)

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