Immunohistochemical study of the sensory formations in the glabrous skin of the rat

The presence of some cytoskeletal proteins related to the intermediate filaments glial fibrillary acidic protein -GFAP and vimentin) and S-100 protein has been investigated in sensory formations of the glabrous skin of the rat. A positive reaction both for S-100 protein and vimentin was found in the inner core and related cells of glomerular and simple sensory corpuscles; in contrast, no positive reaction was shown for GFAP. The authors discuss these results on the basis of the glial origin of the inner core and related cells in sensory formations.     

Local vibrations--mechanical impedance of the human hand's glabrous skin

The mechanical point impedance has been studied in ten different areas of the glabrous skin of the human hand on three male and three female subjects within the frequency range of 20-10 000 Hz. For all tested areas the impedance decreased with increasing frequency down to a minimum value, corresponding to the natural frequency of the skin. After that, the mechanical impedance was directly proportional to the frequency. The highest natural frequency, about 200 Hz, was measured in the distal areas of the finger and the lowest, about 80 Hz, in the proximal areas of the palm (thenar). Small differences in internal damping were also showed to exist. A great amount of handheld tools used in industry have their maximum vibrational levels within the natural frequency range of the skin. In order to avoid adverse effects the skin's mechanical properties should therefore carefully be taken into consideration at designing vibrating tools.     

Localization of mu-opioid receptor 1A on sensory nerve fibers in human skin

Opioid peptides are endogenous neuromodulators that play a major role in the nociceptive pathway by interacting with opioid receptors. So far, four opioid receptors (micro-, delta-, kappa-, orphan-receptor) have been cloned with a wide distribution in the central and peripheral nervous system. In the present study, we give first evidence for the presence of the micro-opioid receptor (MOR) isoform 1A in nerve fibers of human skin. Immunohistochemical analysis revealed MOR immunoreactivity to be present in dermal and epidermal nerve fibers. Double-immunofluorescence staining revealed that MOR is present on calcitonin gene-related protein (CGRP)-positive sensory nerve fibers, while autonomic nerves of blood vessels, hair follicles, or skin glands were negative. In diseased skin such as psoriasis vulgaris, atopic dermatitis, and prurigo nodularis, distribution of MOR 1A immunoreactivity was similar to that of normal skin. These findings expand our knowledge about a direct regulatory role of cutaneous opioid receptors in the skin. Thus, peripheral cutaneous opioid receptors may be involved in the transmission of pain and pruritus, respectively. This is supported by previous observation that opioid receptor antagonists may significantly diminish experimentally evoked histamine-induced itch of the skin. Together, our findings contribute to the understanding of the high antipruritic potency of opioid receptor antagonists in various skin and systemic diseases.     

Influence of isometric exercise on blood flow and sweating in glabrous and nonglabrous human skin.

The distribution of the reflex effects of isometric exercise on cutaneous vasomotor and sudomotor function is not clear. We examined the effects of isometric exercise by different muscle masses on skin blood flow (SkBF) and sweat rate (SR) in nonglabrous skin and in glabrous skin. The latter contains arteriovenous anastomoses (AVAs), which cause large fluctuations in SkBF. SkBF was measured by laser-Doppler flowmetry (LDF) and reported as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). SR was measured by capacitance hygrometry. LDF and SR were measured at the sole, palm, forearm, and ventral leg during separate bouts of isometric handgrip (IHG) and isometric leg extension (ILE). CVC and its standard deviation decreased significantly during IHG and ILE in the palm and sole (P < 0.05) but not in the forearm or leg (P > 0.05). Only palmar SR increased significantly during IHG and ILE (P < 0.05). We conclude that the major reflex influences of isometric exercise on the skin include AVAs and palmar sweat glands and that this is true for both arm and leg exercise.     

Morphology, distribution, and density of sensory receptors in the glabrous skin of the cat rhinarium

The sensory organization of the cat rhinarium has been investigated. Individual rete pegs were found to contain a triad of receptors comprising free nerve endings ascending in the peg to terminate in close proximity to the skin surface, a basally situated layer of Merkel corpuscles, and an abundance of encapsulated receptors lying at the base and to one side of the rete peg. Neither the Merkel corpuscles nor the encapsulated receptors were evenly distributed. Merkel corpuscles were more abundant dorsally; ventrally they were fewer and asymmetrically arranged within individual rete pegs. The encapsulated corpuscles were more evenly distributed, but dorsally they were consistently present as encapsulated clusters of up to nine corpuscles.     

Immunohistochemical study of neuropeptide Y-containing nerve fibers in the human clitoris and penis

The occurrence and distribution of neuropeptide Y in the human clitoris and penis was investigated by light immunohistochemistry. Neuropeptide Y-containing nerve fibers were detected in the tunicae of arteries and veins as well as among trabecular smooth muscle. The distribution pattern of the peptide was similar in both organs although a higher density of immunoreactive nerve fibers was detected in the penis. The immunolocalization of neuropeptide Y was also compared with that of neuron-specific enolase, a neuronal marker which labels the entire nerve network. It is suggested that neuropeptide Y is involved in the physiology of the penis and the clitoris, affecting vascular and nonvascular smooth muscle activity.     

Immunohistochemical study on the expression of c-Fos and c-Jun in human skin wounds

An immunohistochemical study on the temporal expression of c-Fos and c-Jun, both of which designate proto-oncogene products, was performed on 60 human skin wounds with different post-infliction intervals. In unwounded skin, c-Fos or c-Jun was immunolocalized at the nuclei of the epidermal cells in the basal layer, hair follicle cells and sweat gland cells. During the early inflammatory phase of wound healing, the nuclei of polymorphonuclear cells (probably neutrophils), mainly infiltrating at the wound site, were labeled with anti-c-Fos or -c-Jun antibody. As the wound age increased, the neutrophils had disappeared at the wound site, and both mononuclear cells (probably macrophages) and spindle-shaped fibroblastic cells, which expressed a c-Fos or c-Jun positive reaction in the nuclei, were mainly observed. Morphometrically, the distribution of the c-Fos-positive ratio was very similar to that of the c-Jun-positive ratio; the positive ratio was considerably increased in wound specimens with a post-infliction interval of 1 day, thus indicating the late inflammatory or proliferative phase. This study showed that c-Fos and c-Jun were closely involved in the inflammatory phase as well as the proliferative phase of the wound healing process.     

Immunohistochemical study of human pterygium

The purpose of this study has been to evaluate the immunohistochemical characteristics of human pterygial tissues in order to ascertain the possible contribution of an immunological mechanism in the pathogenesis of pterygium and to investigate the presence in the pterygial tissues of some melanoma-associated antigens, in order to evaluate if there may be a small possibility of correlation of the two diseases. Human biopsy specimens of pterygium were obtained by surgery for pterygium excision. Tissue segments were fixed and processed for paraffin embedding. Microtome sections were treated for the immunohistochemical demonstration of IgA, IgM, IgG, CD3, CD20, CD68, HLA-DR, Protein S100, HMB45, and Melan A using the avidin-biotin peroxidase method or the streptavidin biotin-alkaline phosphatase method. The findings suggest that all the effector components of the mucosal immune system are present in the human pterygium and, among the most sensitive markers for melanoma, only S100 shows immunoreactivity. An immunopathogenetic mechanism seems to be responsible for the pathogenesis of pterygium, perhaps being caused by pre-existing conjunctivitis or microtrauma in combination with the patient's predisposition. No correlation between pterygium and melanoma was found.     

A variation of pigmentation in the glabrous skin of dogs

The usual pigmentation pattern in mammalian skin consists of fixed melanocytes in the basal layer of the epidermis, supplying keratinocytes with melanosomes. We observed that the glabrous skin (rhinaria and footpads) of dogs deviates from this pattern. In dogs, melanocytes are found in both the dermis and epidermis. The epidermal melanocytes are situated in the intercellular spaces of the basal and spinous layers. They are characterized by a quantity of cytoplasm containing a centriole, also developing melanosomes, and in some cases annulate lamellae. There is a high frequency of closely apposed melanocytes in the epidermis. Melanosomes in different stages of formation are also abundant. The morphology of the glabrous skin of dogs suggests transport of melanocytes from the dermis into the epidermis and formation of melanosomes in the epidermis. A distributed and intense pigment formation may be necessary to achieve the black noses of many dog breeds and wild canids, as well as dark footpads despite heavy abrasion and rapid skin renewal.     

Estimation of the conduction velocity distribution of human sensory nerve fibers.

A new method for estimating the distribution of conduction velocities (DCV) of peripheral nerve fibers has been developed. It also enables estimation of single nerve fiber action potential (SFAP), which agrees with the physiological knowledge. Two compound nerve action potentials (CAPs) elicited by electrical stimulation of a nerve bundle were recorded at different conduction distances. The distances between the stimulation and recording electrodes were measured on the skin surface along the nerve bundle. Starting with an arbitrary SFAP, the first estimated DCV was calculated from a CAP by the regularized non-negative least squares method. The next SFAP was then calculated by deconvolution of the other CAP and the estimated DCV. A lowpass filter with an appropriate cutoff frequency was used to obtain better conversion. The process was iterated until the CAP error defined as /CAP(calculated)-CAP/(2) was small enough. The conduction distances contained errors in measurement, especially in the distal segment, that distorted the estimated results. The Fibonacci search, therefore, was adopted to optimize the distance according to the CAP error. The accuracy of this method was demonstrated by a simulation study performed with two CAPs calculated from an arbitrary bimodal DCV and a biphasic SFAP to which a Gaussian white noise was added. The reliability of this method was checked in normal subjects by recording a pair of CAPs elicited by stimulation of the median nerve at the wrist and the elbow.     

Tactile receptor discharge and mechanical properties of glabrous skin

Current knowledge of the functional properties of mammalian cutaneous mechanoreceptors is reviewed with special reference to receptors associated with the glabrous skin of the raccoon and squirrel monkey hand. Four physiologically defined mechanoreceptor types are recognized: Pacinian afferents, rapidly adapting (RA), and slowly adapting type I (SAI), and slowly adapting type II (SAII). The SAI category is divided into moderately slowly adapting and very slowly adapting (VSA) types in terms of the duration of their response to a prolonged mechanical displacement of skin. Although both RA and SA units are capable of signaling displacement ramp velocity, the pattern of discharge during ramp stimulation may vary widely among units. SAI units also code the depth of skin displacement, but there is no best-fitting function describing the relationship. Static discharge is also markedly influenced by prior ramp velocity. Both raccoon and squirrel monkey VSA units show wide variation in the regularity of their discharge during static displacement. The rate of adaptation of SAI units is less when constant force stimuli are applied to the skin than when constant displacement stimuli are applied. This is partly attributable to mechanical properties of the skin. When either constant force or constant displacement stimuli are spaced too closely in time, there is a progressive (trial-to-trial) decrement in response rate, accounted for in part by failure of the skin to recover to its initial resting level.     

Distribution of neurofilament-immunoreactive nerve fibers in human skin

Neurofilament immunoreactive nerve fibers were demonstrated in human skin using indirect immunohistochemical technique with antibodies to neurofilament polypeptides. Neurofilament-positive fibers were seen as free nerve endings in the epidermis and in dermal papilla, in Meissner's corpuscles and as fibers crossing in the dermis. Strongly fluorescent nerve fibers were also seen around hair follicles, sweat gland ducts and sometimes in relation to blood vessels. From the distribution pattern it was concluded that predominantly sensory nerve fibers were labelled and that this technique may be used to study reinnervation of cutaneous sensory nerves following traumatic injuries and surgical procedures.     

Distribution of neurofilament-immunoreactive nerve fibers in human skin

Summary Neurofilament immunoreactive nerve fibers were demonstrated in human skin using indirect immunohistochemical technique with antibodies to neurofilament polypeptides. Neurofilament-positive fibers were seen as free nerve endings in the epidermis and in dermal papilla, in Meissner's corpuscles and as fibers crousing in the dermis. Strongly fluorescent nerve fibers were also seen around hair follicles, sweat gland ducts and sometimes in relation to blood vessels. From the distribution pattern it was concluded that predominantly sensory nerve fibers were labelled and that this technique may be used to study reinnervation of cutaneous sensory nerved following tramatic injuries and surgical procedures.     

Neuropeptides of the primary sensory neurones in rat skin: an ontogenic study.

Cutaneous primary sensory neurones contain a number of biologically-active peptides, including substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP). However, little information is available on ontogenic changes in the tissue concentrations of these neuropeptides. In this study, the concentrations of these neuropeptides have been assessed in dorsal and ventral abdominal rat skin at various stages of development from foetal, early neonatal, late neonatal, weaner to adult, using sensitive and specific radioimmunoassays. In addition, the levels of peptide histidine isoleucine (PHI), a peptide found in non-sensory cutaneous nerves, were assessed to control the study. The levels of PHI and NKA immunoreactivity did not change significantly at any stage of development. However, the levels of SP and CGRP immunoreactivity were significantly elevated in the early neonate with CGRP remaining elevated in the late neonate. The levels of both SP and CGRP were not significantly different between other developmental groups. Significant elevations in cutaneous SP and CGRP concentrations in early neonatal life in the rat, at a time when the pups are blind and naked, may be related to control of cutaneous sensitivity, which during this period of development, has positive survival value for the pups.