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The innervation of Meissner's corpuscles (Mc) is complex, consisting of different types of sensory nerve fibers. We investigated the neurochemistry of Mc in human digital skin by indirect immunofluorescence, using a wide panel of both general neuronal as well as neurotransmitter-related molecules. Structural proteins (protein gene product 9.5, neuron-specific enolase, neurofilament) were found to consistently label the entire neuronal component of Mc. Immunoreactivity for gamma-melanocyte stimulating hormone was detected in the large diameter fibers running spirally within the corpuscles, while a number of peptide transmitters (substance P, calcitonin gene-related peptide, neurokinin A, galanin, somatostatin) were found in the thin unmyelinated fibers in both intra- and extracorpuscular locations.

Cutaneous nerve fibers can modulate inflammatory reactions through local release of neuro-peptides (NP). In fact, NP are able to regulate both acute and chronic aspects of cutaneous inflammatory processes, such as vascular motility, cellular traffic-king, activation and trophism. Several experimental evidences suggest a participation of NP to the pathogenesis of inflammatory dermatoses: in particular, modulation of inflammatory reactions in the skin can be obtained through pharmacologic manipulation of the neuropeptidergic system. Furthermore, evidence of local alterations of NP levels in inflamed skin has been obtained. It has been hypothesized that the inflammatory process induces reactive changes in the neuronal NP content. The primary candidate as mediator of this neuronal recruitment in the course of inflammatory reactions is the neurotrophin nerve growth factor, that is produced in the skin in increased amounts during inflammatory processes and may regulate peptidergic synthesis at a neuronal level.

Merkel cells (MCs) are specialized sensory cells widely distributed in the epithelia of vertebrates. A variable immunohistochemical pattern of neuronal and neurotransmitter markers has been demonstrated in MCs of several species including man. In the present study, we investigated the expression of neurochemical markers in a selected population of human cutaneous MCs by immunofluorescence. The structural neural proteins protein gene product 9.5 and neuron-specific enolase were found to be the most reliable markers for MC identification. Moreover, neurofilament immunoreactivity was shown in a small subset of epidermal MCs. Among the neurotransmitter markers, evidence for expression of calcitonin gene-related peptide, vasoactive intestinal polypeptide, peptide histidine isoleucine amide, neuropeptide Y, neurokinin A, galanin, substance P, somatostatin and phenylethanolamine N-methyltransferase was found. These immunoreactivities were highly variable as far as number of positive cells and staining intensity were concerned. The results indicate that a complex and heterogeneous immunophenotype can be expressed even within a homogeneous population of human MCs.

Background: The innervation of the oral mucosa has so far been studied mainly by histochemical and ultrastructural techniques. Only few studies have investigated the presence of neural proteins and neurotransmitters in human gingival mucosa., Objective: The purpose of the present study was to evaluate the presence and distribution of neural structural and transmitter proteins in different areas of normal human oral mucosa., Method: Indirect immunofluorescence was employed on specimens taken from different mucosal regions (gingiva, lips, gums, palate). Both structural (low-affinity nerve growth factor receptor, NGFr; protein gene product 9.5, PGP 9.5) and neuropeptide markers (substance P; calcitonin gene-related peptide; vasoactive intestinal peptide, neuropeptide Y) were used., Results: NGFr and PGP 9.5 intensely labelled both nerve fibres and selected epithelial cells, while neuropeptide immunoreactivity was scarcely expressed and exclusively localized in nerve fibres., Conclusions: Similarly in the distribution pattern and neurochemistry between oral and cutaneous innervation is apparent. Expression of NGFr could be relevant to the trophism of both the oral innervation and epithelium.

Neuropeptides (NP) are protein compounds contained both in the central and peripheral nervous system. They can be antidromically released from sensory nerves and are implicated in the so-called neurogenic inflammation. They also exert a number of functions within the immune system and are thought to act as trophic as well as mitogenic substances. Several NP have been detected in human skin by immunohistochemical and radioimmunological techniques, and recent reports have demonstrated that NP could be involved in the mechanisms of certain dermatoses. The involvement of NP in either physiological or pathophysiological skin conditions is discussed. Moreover, a few questions, which still need to be addressed, are raised, and future directions this field of research should take are outlined.

The distribution and localization of several neuropeptides were investigated in the lichenified lesions of 11 patients with atopic dermatitis using indirect immunofluorescence. Substance P-positive nerve fibres were observed in most of the cases of atopic dermatitis, but not in normal controls. Somatostatin immunoreactive nerves were not found in the skin of atopic dermatitis, whereas a normal pattern of immunoreactivity could be detected in most of the healthy subjects. Neuropeptide Y-positive dendritic epidermal cells were observed in lesional skin from patients with atopic dermatitis, but not in controls. Calcitonin gene-related peptide and vasoactive intestinal polypeptide immunoreactivity in patients with atopic dermatitis did not differ from that in healthy subjects. With galanin antiserum a diffuse intracellular staining was observed in the epidermis of both atopic patients and controls, while no positive staining was found with either neurotensin or neurokinin A antibodies in either group. These findings suggest a possible involvement of some neuropeptides in the pathomechanisms of atopic dermatitis.

There is increasing evidence that neuropeptides (NP) such as substance P (SP) and vasoactive intestinal polypeptide (VIP) are involved in the pathogenesis of atopic dermatitis (AD). Vasoactive intestinal polypeptide levels were found to be significantly elevated in lesional skin of AD as compared to controls. We evaluated by radioimmunoassay the SP content in whole skin homogenates from chronic lichenified lesions of patients with AD. The levels of SP were significantly decreased in lesional skin from AD patients as compared to control skin (0.25 ± 0.03 vs. 0.97 ± 0.24 pmol/g tissue, p < 0.01). The diminished SP levels as opposed to increased VIP concentrations could be consistent with different roles of these NP as modulatory agents in the mechanisms associated with AD. [ABSTRACT FROM AUTHOR]