Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus

Abstract

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.

IL-33 augments substance P–induced VEGF secretion from human mast cells and is increased in psoriatic skin

“…Use of biotinylated SP suggested that NK-1 expression may be increased in keratinocytes from psoriatic plaques (71). Another study showed mast cells express the NK-1 receptor in both affected and unaffected psoriatic skin (6). NK-1 is also important in stress-induced murine skin mast cell activation (3,16), and in the development of atopic dermatitis in mice (68).…”

“…Neuropeptides (5), especially SP, could be involved in the pathogenesis of inflammatory skin disorders, such as psoriasis (6,7), characterized by increased epidermal vascularization, keratinocyte hyperproliferation, and inflammation (8). SP-positive nerve fibers are more dense in psoriatic lesions and have an increased number of mast cell contacts compared with normal skin (9)(10)(11)(12).…”

Psychological and biological background of the interaction between psoriasis and stress

“…A kilenc, alapkortizolszintet vizsgáló tanulmányból öt alacsonyabb plazma-vagy nyálhormon-koncentrációt mutatott ki [16,53,54,55,56,57,58,59,60]. Tudva, hogy a HPA-tengely működését és így a kortizoltermelést fokozó IFN-γ, TNF-α, IL-10, IL-12 és IL-18 plazmaszintjei emelkedettek pikkelysömörben, a megfi gyelt alacsony stresszhormon-koncentráció diszfunkcionális HPA-tengely-működést sejtet [61].…”

Stress Hormone and Skin Disease

“…SP, one of the stress neuropeptides, is suggested to have a role of neurogenic inflammation in the pathogenesis of psoriasis. Expression of SP and its receptor correlated with the severity of depression and was associated with low level of cortisol, which indicates chronic stress (Remröd C et al, 2007;Amatya et al, 2011). SP also play a critical role in stressinduced mast cell degranulation in mice .…”