Substance P alterations in skin and brain of chronically stressed atopic-like mice.

BACKGROUND: Stress is known to worsen the symptoms of atopic eczema (AE). Substance P is likely to play an important role in the development and pathogenesis of AE. OBJECTIVE: To examine a possible connection between chronic mild stress and changes in the expression of substance P and its receptor (R) neurokinin (NK) 1 in the skin and stress-related brain regions in NC/Nga atopic-like mice. METHODS: The mice were divided into three groups (eight animals per group): SE (stressed eczematous), NSE (non-stressed eczematous) and SC (stressed control). Ears and brains of the mice were investigated using immunohistochemistry and RT-PCR. RESULTS: In the skin, there was a decrease in the number of substance P immunoreactive nerve fibres in SE compared with SC group. RT-PCR showed a strong tendency to an increase in mRNA for NK1R in the skin of SE compared with NSE mice. There was an increase in the number of mast cells and the degree of their degranulation in the SE compared with both other groups. A decrease in substance P immunoreactivity in medial hippocampus was found in SE compared with NSE animals. In prefrontal cortex and central amygdala, there were no significant differences in substance P immunoreactivity between the three groups. CONCLUSION: Exposure to chronic mild stress in NC/Nga atopic-like mice may result in altered expression patterns of substance P in the skin and hippocampus.

Neuroimmune mechanisms in patients with atopic dermatitis during chronic stress.

OBJECTIVE: To identify pathoaetiological neuroimmune mechanisms in patients with atopic dermatitis (AD) and chronic stress, focusing at nerve density, sensory neuropeptides, and the serotonergic system. METHODS: Eleven patients with AD with histories of stress worsening were included. Biopsies from involved and non-involved skin were processed for immunohistochemistry. Salivary cortisol test was done as a marker for chronic stress. RESULTS: There were more acanthosis and fewer nerve fibres in epidermis and papillary dermis of involved compared with non-involved skin. Whereas there was no significant change in the number of substance P and calcitonin gene-related peptide-positive nerve fibres between the involved and non-involved skin, there was an increase in the epidermal fraction of 5-hydroxtrytamine 1A (5-HT1A) receptor and serotonin transporter protein (SERT) immunoreactivity in the involved skin. The number of 5-HT2AR, CD3-positive cells, and SERT-positive cells, most of them being CD3 positive, was increased in involved skin. There was an increase in mast cells in the involved skin, and these cells were often located close to the basement membrane. There was a strong tendency to a correlation between 5-HT2AR positive cells in the papillary dermis of involved skin and low cortisol ratios, being an indicator of chronic stress. CONCLUSION: A changed innervation and modulation of the serotonergic system are indicated in chronic atopic eczema also during chronic stress.

Upregulation of the axonal growth and the expression of substance P and its NK1 receptor in human allergic contact dermatitis.

Nerve fibers and sensory neuropeptides substance P and calcitonin gene-related peptide (CGRP) have been reported to be involved in allergic contact dermatitis (ACD). In the present study, we investigated the general innervation (using antibody against protein gene product 9.5, PGP 9.5), axonal growth (using antibody against growth associated protein, GAP-43), CGRP, and substance P with its receptor neurokinin 1 (NK1), in positive epicutaneous reactions to nickel sulphate from nickel-allergic patients, at the peak of inflammation, 72 hr after challenge with the antigen. There was an increased (p < 0.01) number of GAP-43 positive fibers in the eczematous compared with control skin, indicating an increased axonal growth already at 72 hr postchallenge. Double staining revealed a coexpression of CGRP and GAP-43 on dermal nerve fibers. There was no difference in the number of substance P and CGRP positive nerve fibers between eczematous and control skin. However, semiquantification analyses showed an increased expression of substance P positive inflammatory cells, being CD3, CD4, or CD8 positive, and NK1R positive inflammatory cells, being tryptase or CD3 positive. These results indicate a contribution of regenerating nerve fibers and substance P to the contact allergic reaction.

Patients with visual display unit-related facial symptoms are stingers.

Thirty patients without obvious skin disease but with subjective skin symptoms related to work with visual display units (VDUs) and 32 healthy persons were single-blind-tested with a solution of 5% lactic acid and pure water on their cheeks. Thirteen of the patients and 6 control persons reacted positively as "stingers" (p < 0.05) in this objective test of sensitive skin. The reason why some patients react with subjective symptoms like itching, burning, stinging, prickling or tingling is unclear. The result of this study, that patients with VDU-related skin symptoms have sensitive skin, does not tell anything about the aetiology of the symptoms. Former studies speak against the role of electric and magnetic fields and indicate that "techno-stress", cognitive factors or flickering from the VDUs or fluorescent tubes could be of importance, as could the Swedish mass media debate.

Stinging and rosacea.

A total of 32 rosacea patients (25 with the papulopustular type of rosacea and 7 with the erythematotelangiectatic type) and 32 healthy persons were single-blind tested with a solution of 5% lactic acid and pure water applied to their cheeks. Twenty-four patients and 6 controls reacted positively as "stingers" (p<0.001) in this objective test of sensitive skin. All 7 of the patients with erythematotelangiectatic rosacea, but only 17/25 with the papulopustular type, were stingers (n.s.). The reason why some patients react with subjective symptoms, such as itching, burning, stinging, prickling or tingling, is unclear. The findings in this study are not surprising, but do support the theory that impairment due to different stimuli, most likely because of vascular sensitivity, is a central mechanism in the aetiology of rosacea. The correlation between sensitive vessels and sensitive skin has, however, not yet been determined.