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

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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.

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References

  1. Al’Abadie MS, Senior HJ, Bleehen SS, Gawkrodger DJ (1995) Neuropeptides and general neuronal marker in psoriasis—an immunohistochemical study. Clin Exp Dermatol 20:384–389

    Article  PubMed  CAS  Google Scholar 

  2. Anand P, Springall DR, Blank MA, Sellu D, Polak JM, Bloom SR (1991) Neuropeptides in skin disease: Increased VIP in eczema and psoriasis but not axillary hyperhidrosis. Br J Dermatol 124:547–549

    Article  PubMed  CAS  Google Scholar 

  3. Benrath J, Zimmermann M, Gillardon F (1995) Substance P and nitric oxide mediate wound healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation. Neurosci Lett 200:17–20

    Article  PubMed  CAS  Google Scholar 

  4. Chan J, Smoller BR, Raychauduri SP, Jiang WY, Farber EM (1997) Intraepidermal nerve fiber expression of calcitonin gene-related peptide, vasoactive intestinal peptide and substance P in psoriasis. Arch Dermatol Res 289:611–616

    Article  PubMed  CAS  Google Scholar 

  5. Erin N, Ersoy Y, Ercan F, Akici A, Oktav S (2004) NK-1 antagonist CP99994 inhibits stress-induced mast cell degranulation in rats. Clin Exp Dermatol 29:644–648

    Article  PubMed  CAS  Google Scholar 

  6. Gaspari AA (2006) Innate and adaptive immunity and the pathophysiology of psoriasis. JAAD 54:67–80

    Google Scholar 

  7. Griffiths CEM, Richards HL (2001) Psychological influences in psoriasis. Clin Exp Dermatol 26:338–342

    Article  PubMed  CAS  Google Scholar 

  8. Harvima IT, Viinamaki H, Naukkarinen A, Paukkonen K, Neittaanmaki H, Harvima RJ, Horsmanheimo M (1993) Association of cutaneous mast cells and sensory nerves with psychiatric stress in psoriasis. Psychoter Psychosom 60:168–176

    Article  CAS  Google Scholar 

  9. Jiang WY, Raychaudhuri SP, Farber EM (1998) Double-labelled immunoflourescence study of cutaneous nerves in psoriasis. Int J Dermatol 37:572–574

    Article  PubMed  CAS  Google Scholar 

  10. Mantyh PW (2002) Neurobiology of substance P and the NK-1 receptor. J Clin Psychiatry 63:6–10

    PubMed  CAS  Google Scholar 

  11. Nakamura M, Toyoda M, Morohashi M (2003) Pruritogenic mediators in psoriasis vulgaris: comparative evaluation of itch-associated cutaneous factors. Br J Dermatol 149:718–730

    Article  PubMed  CAS  Google Scholar 

  12. Nakano Y (2004) Stress-induced modulation of skin immune function: two types of antigen-presenting cells in the epidermis are differentially regulated by chronic stress. Br J Dermatol 151:50–64

    Article  PubMed  CAS  Google Scholar 

  13. Naukkarinen A, Harvima I, Paukkonen K, Aalto ML, Horsmanheimo M (1993) Immunohistochemical analysis of sensory nerves and neuropeptides, and their contacts with mast cells in developing a mature psoriatic lesion. Arch Dermatol Res 285:341–346

    Article  PubMed  CAS  Google Scholar 

  14. Naukkarinen A, Harvima IT, Aalto ML, Horsmanheimo M (1994) Mast cell tryptase and chymase are regulators of neurogenic inflammation in psoriatic skin. Int J Dermatol 33:361–366

    Article  PubMed  CAS  Google Scholar 

  15. Naukkarinen A, Jarvikallio A, Lakkakorpi J, Harvima IT, Harvima RJ, Horsmanheimo M (1996) Quantitative histochemical analysis of mast cells and sensory nerves in psoriatic skin. J Pathol 180:200–205

    Article  PubMed  CAS  Google Scholar 

  16. Ohmura T, Tsunenari I, Hayashi T, Satoh Y, Konomi A, Nanri H, Kawashi M, Morikawa M, Kadota T, Satoh H (2004) Role of substance P in an NC/Nga mouse model of atopic dermatitis-like disease. Int Arch Allergy Immunol 133:389–397

    Article  PubMed  CAS  Google Scholar 

  17. Pincelli C, Fantini F, Romualdi P, Sevignani C, Lesa G, Benassi L, Gianetti A (1992) Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes. J Invest Dermatol 98:421–427

    Article  PubMed  CAS  Google Scholar 

  18. Pincelli C, Fantini F, Giardino L, Zanni M, Calza L, Sevignani C, Gianetti A (1993) Autoradiographic detection of substance P receptors in normal and psoriatic skin. J Invest Dermatol 101:301–304

    Article  PubMed  CAS  Google Scholar 

  19. Pothoulakis C, Castagliuolo I, Leeman SE, Wang CC, Li H, Hoffman BJ, Mezey E (1998) Substance P receptor expression in intestinal epithelium in Clostridium difficile toxin A enteritis in rats. Am J Physiol(Gastrointest Liver Physiol) 275:G68–75

    CAS  Google Scholar 

  20. Raychaudhuri SP, Alto P, Farber EM (2000) Neuroimmunologic aspects of psoriasis. Cutis 66:357–362

    PubMed  CAS  Google Scholar 

  21. Raychaudhuri SP, Sanyal M, Weltman H, Kundu-Raychaudhuri S (2004) K252a, a high-affinity nerve growth factor receptor blocker, improves psoriasis: an in vivo study using the severe combined immunodeficient mouse-human skin model. J Invest Dermatol 122:812–819

    Article  PubMed  CAS  Google Scholar 

  22. Reich A, Szepietowski JC, Wisnicka B, Pacan P (2003) Does stress influence itching in psoriatic patients? Dermatol Psychosom 4:151–155

    Article  Google Scholar 

  23. Rosmond R, Dallman MF, Björntorp P (1998) Stress-related cortisol secretion in men: relationships with abdominal obesity and endocrine, metabolic and hemodynamic abnormalities. J Clin Endocrinol Metab 83:1853–1859

    Article  PubMed  CAS  Google Scholar 

  24. Singh LK, Pang X, Alexacos N, Letourneau R, Theoharides TC (1999) Acute immobilization stress triggers skin mast cell degranulation via corticotropin releasing hormone, neurotensin and substance P. A link to neurogenic skin disorders. Brain Behav Immun 13:225–239

    Article  PubMed  CAS  Google Scholar 

  25. Staniek V, Doutremepuich JD, Schmitt D, Claudy A, Misery L (1999) Expression of substance P receptors in normal and psoriatic skin. Pathobiology 67:51–54

    Article  PubMed  CAS  Google Scholar 

  26. Szepietowski JC, Reich A, Wisnicka B (2004) Pruritus and psoriasis. Br J Dermatol 151:1284

    Article  PubMed  CAS  Google Scholar 

  27. Theoharides TC, Cochrane DE (2004) Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol 146:1–12

    Article  PubMed  CAS  Google Scholar 

  28. Toyoda M, Makino T, Kagoura M, Morohashi M (2000) Immunolocalization of substance P in human skin mast cells. Arch Dermatol Res 292:418–421

    Article  PubMed  CAS  Google Scholar 

  29. Toyoda M, Nakamura M, Nakada K, Nakagawa H, Morohashi M (2005) Characteristic alterations of cutaneous neurogenic factors in photoaged skin. Br J Dermatol 153(suppl 2):13–22

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by grants from the Swedish Psoriasis Association, the Welander/Finsen Foundation, and from the Karolinska Institute. The technical assistance of Anna-Lena Kastman, BMA, is gratefully acknowledged.

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Correspondence to Klas Nordlind.

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Remröd, C., Lonne-Rahm, S. & Nordlind, K. Study of substance P and its receptor neurokinin-1 in psoriasis and their relation to chronic stress and pruritus. Arch Dermatol Res 299, 85–91 (2007). https://doi.org/10.1007/s00403-007-0745-x

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  • DOI: https://doi.org/10.1007/s00403-007-0745-x

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