Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin

Wang, Lixin; Hilliges, Marita; Jernberg, Tomas; Wiegleb-Edström, Desiree; Johansson, Ӧlle

doi:10.1007/bf00329435

Cited by 233 publications

(149 citation statements)

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“…Biopsies are taken from the distal leg (DL), 10 cm above the lateral malleolus, and the proximal thigh (PT), 20 cm below the anterior iliac spine 9 . All IENF are labeled using protein gene product 9.5 (PGP), a pan neuronal marker [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

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Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies

Dauch

Lindblad

Hayes

et al. 2013

JoVE

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A punch biopsy of the skin is commonly used to quantify intraepidermal nerve fiber densities (IENFD) for the diagnosis of peripheral polyneuropathy 1,2 . At present, it is common practice to collect 3 mm skin biopsies from the distal leg (DL) and the proximal thigh (PT) for the evaluation of length-dependent polyneuropathies 3 . However, due to the multidirectional nature of IENFs, it is challenging to examine overlapping nerve structures through the analysis of two-dimensional (2D) imaging. Alternatively, three-dimensional (3D) imaging could provide a better solution for this dilemma.In the current report, we present methods for applying 3D imaging to study painful neuropathy (PN). In order to identify IENFs, skin samples are processed for immunofluorescent analysis of protein gene product 9.5 (PGP), a pan neuronal marker. At present, it is standard practice to diagnose small fiber neuropathies using IENFD determined by PGP immunohistochemistry using brightfield microscopy 4 . In the current study, we applied double immunofluorescent analysis to identify total IENFD, using PGP, and nociceptive IENF, through the use of antibodies that recognize tropomyosin-receptor-kinase A (Trk A), the high affinity receptor for nerve growth factor 5 . The advantages of co-staining IENF with PGP and Trk A antibodies benefits the study of PN by clearly staining PGP-positive, nociceptive fibers. These fluorescent signals can be quantified to determine nociceptive IENFD and morphological changes of IENF associated with PN. The fluorescent images are acquired by confocal microscopy and processed for 3D analysis. 3D-imaging provides rotational abilities to further analyze morphological changes associated with PN. Taken together, fluorescent co-staining, confocal imaging, and 3D analysis clearly benefit the study of PN. Video LinkThe video component of this article can be found at

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Section: Introductionmentioning

confidence: 99%

“…At present, it is standard practice to diagnose small fiber neuropathies using IENFD determined by PGP staining with brightfield microscopy 6 . Additionally, several research groups have used immunofluorescent protocols for PGP immunohistochemistry [7][8][9] . Small fiber neuropathy is commonly associated with neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies

Dauch

Lindblad

Hayes

et al. 2013

JoVE

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“…Sympathetic fibers travel together with sensory nerve fibers to innervate blood vessels, sweat glands, and hair follicles (20). They also appear as single nerve fibers in the dermis and epidermis (21)(22)(23). Because the nerve fibers present in the skin release classical neurotransmitters, we examined whether catecholaminergic neurotransmission affects the immunocompetent cells of the skin.…”

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confidence: 99%

Catecholamines Inhibit the Antigen-Presenting Capability of Epidermal Langerhans Cells

Seiffert¹,

Hosoi²,

Torii³

et al. 2002

The Journal of Immunology

119

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The sympathetic nervous system modulates immune function at a number of levels. Within the epidermis, APCs (Langerhans cells (LC)) are frequently anatomically associated with peripheral nerves. Furthermore, some neuropeptides have been shown to regulate LC Ag-presenting function. We explored the expression of adrenergic receptors (AR) in murine LC and assessed their functional role on Ag presentation and modulation of cutaneous immune responses. Both purified LC and the LC-like cell lines XS52-4D and XS106 expressed mRNA for the ARs α1A and β2. XS106 cells and purified LC also expressed β1-AR mRNA. Treatment of murine epidermal cell preparations with epinephrine (EPI) or norepinephrine inhibited Ag presentation in vitro. Furthermore, pretreatment of epidermal cells with EPI or norepinephrine in vitro suppressed the ability of these cells to present Ag for elicitation of delayed-type hypersensitivity in previously immunized mice. This effect was blocked by use of the β2-adrenergic antagonist ICI 118,551 but not by the α-antagonist phentolamine. Local intradermal injection of EPI inhibited the induction of contact hypersensitivity to epicutaneously administered haptens. Surprisingly, injection of EPI at a distant site also suppressed induction of contact hypersensitivity. Thus, catecholamines may have both local and systemic effects. We conclude that specific ARs are expressed on LC and that signaling through these receptors can decrease epidermal immune reactions.

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“…Tel. : (49) (6131) 39 34 94 ; fax : (49) (6131) 39 54 01 ; e-mail : tmueller!mail.uni-mainz.de (PGP 9.5) was found to be suitable for the demonstration of intraepidermal nerve fibres in the skin (Wang et al 1990). By means of this procedure Rice et al (1993) succeeded in visualising intraepidermal nerve fibres in the intervibrissal fur of the rat.…”

Section: mentioning

confidence: 99%

Characteristic intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat: morphological details revealed by intravital methylene blue staining and the zinc iodide‐osmium tetroxide technique

Müller

1999

Journal of Anatomy

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Light microscopic observations employing intravital methylene blue staining and impregnation by the zinc iodide-osmium tetroxide technique are presented for intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat snout. Both procedures revealed anatomical details of the intraepidermal nerve fibre plexus in epidermal hillocks often located very close to the mouths of hairs. These nerve fibres appeared to resemble those described in previous immunohistochemical studies as cluster or bush endings. The methylene blue preparations demonstrated the existence of an intensely stained enlargement at the site of the branching point of the nerve fibres which seemed to be functionally related to the development of such nerve fibre plexuses. Due to their close association with hairs, these nerve fibre plexuses are most likely to be mechanoreceptive. Additionally, solitary varicose nerve fibres were found loosely distributed within the epidermis. The visualisation of 2 different morphological types of nerve fibre endings extends the validity of the concept of punctate sensibility into the epidermis. Methylene blue staining appeared to be somewhat superior to the zinc iodide-osmium tetroxide technique. Due to their selectivity for intraepidermal nerve fibres, the methods applied here supplement immunohistochemical procedures in a helpful manner.Key words : Skin ; hair ; mechanoreception ; thermoreception ; nociception. The mystacial pad on the snout of the rat is endowed with rows of long, densely innervated tactile hairs referred to as vibrissae. The intervibrissal fur is composed of an epidermis, dermis, numerous follicles of guard and vellus hairs, and the papillary muscle slings for the protraction of the vibrissal follicle-sinus complexes. Earlier attempts to visualise the epidermal innervation of the intervibrissal fur were unsuccessful because silver impregnation, one of the classic neuroanatomical techniques for studying peripheral nerve fibres, failed (Rice & Munger, 1986). Subsequently, immunohistochemistry for protein gene product 9. (PGP 9.5) was found to be suitable for the demonstration of intraepidermal nerve fibres in the skin (Wang et al. 1990). By means of this procedure Rice et al. (1993) succeeded in visualising intraepidermal nerve fibres in the intervibrissal fur of the rat. In addition to solitary free nerve endings, clusters of intraepidermal nerve fibres were detected, displayed by accumulations of immunofluorescence, although the morphological details of the arrangement of the axon terminals were not demonstrated. Later, Fundin et al. (1994) described larger bush-like endings in addition to the smaller cluster-like endings by the use of horseradish peroxidase conjugated with wheat germ agglutinin or choleragenoid ; the images showed

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Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin

Cited by 233 publications

References 33 publications

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies

Three-dimensional Imaging of Nociceptive Intraepidermal Nerve Fibers in Human Skin Biopsies

Catecholamines Inhibit the Antigen-Presenting Capability of Epidermal Langerhans Cells

Characteristic intraepidermal nerve fibre endings of the intervibrissal fur in the mystacial pad of the rat: morphological details revealed by intravital methylene blue staining and the zinc iodide‐osmium tetroxide technique

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