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Substance P and its receptor(R) neurokinin (NK)-1 may have a role in the pathogenesis of psoriasis. Stress has been reported to play a role in the onset and exacerbation of psoriasis, which might include the substance P-NK-1 receptor(R) pathway. A feature of psoriasis, that has been correlated to the severity of stress and secretion of substance P, is pruritus. The objective of this study was to investigate the expression of substance P and the NK-1R in involved and noninvolved psoriatic skin, using a biotinylated streptavidin technique. Moreover, a possible correlation between the patient s level of chronic stress, measured by salivary cortisol samples, degree of lesional pruritus, measured by means of a visual analogue scale, and the expression of substance P- and the NK-1R, was investigated. There was a low number of substance P positive nerve fibres in noninvolved and involved skin, the major immunoreactivity for substance P being found in inflammatory cells. The number of substance P- and NK-1R positive inflammatory cells was increased in involved compared to noninvolved psoriatic skin. The substance P positive cells were mostly lymphocytes, while most of the NK-1R positive cells were mast cells. NK-1R immunoreactivity was also seen as a reticular pattern in the upper part of the epidermis of involved skin in the majority of the patients. Low cortisol ratios in the patients, being an indicator of chronic stress, were correlated to an increased number of substance P- and NK-1R positive inflammatory cells in noninvolved psoriatic skin, and higher cortisol ratios to the presence of keratinocyte NK-1R immunoreactivity in involved skin. The degree of pruritus could not be correlated to the number of substance P positive fibers nor cells. Nonneuronal substance P and its receptor NK-1 might have a role in psoriasis, also during chronic stress.

Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P<0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HTlAR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P<0.001 and P<0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P<0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis.

Caroline Svanström,1,2 Sol-Britt Lonne-Rahm,1 Klas Nordlind21Department of Dermatology, Mälarsjukhuset, Eskilstuna, Sweden; 2Department of Medicine, Solna, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm, SwedenCorrespondence: Caroline SvanströmDepartment of Medicine, Solna, Dermatology and Venereology Unit, Karolinska Institutet, Stockholm SE 171 76, SwedenTel +46 70 230 7268Email svanstrom.caroline@gmail.comAbstract: Psoriasis is a chronic inflammatory skin disease that may be triggered or worsened by several factors, including alcohol. A higher than average alcohol consumption is common among individuals with psoriasis. Neurobiological signaling affected by alcohol intake includes a range of neurotransmitters, such as the dopaminergic, serotonergic, and tachykinergic systems, involved in reward and drug-seeking. These neurotransmitters may also have an impact on the inflammatory processes per se in psoriasis. Future therapy may, therefore, be targeted at neurotransmitter networks involved with both alcohol intake and the inflammatory processes.Keywords: psoriasis, alcohol, pruritus, neurotransmitters