{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:12:34Z","timestamp":1791443554650,"version":"4.3.3"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Aprepitant is a neurokinin 1 receptor (NK1R) antagonist used for its antipruritic properties in dermatoses and systemic diseases. The mode of action is still unclear. A peripheral effect is assumed as aprepitant shows efficacy in inflammatory skin diseases including prurigo nodularis (PN<\/jats:styled-content>).<\/jats:p><\/jats:sec>Objectives<\/jats:title>To investigate the peripheral effects of NK<\/jats:styled-content>1R antagonism in PN<\/jats:styled-content> and cell culture models.<\/jats:p><\/jats:sec>Methods<\/jats:title>Subjects with PN<\/jats:styled-content> received an aprepitant treatment. Clinical, morphological and immunohistochemical changes were investigated in skin biopsies before and after treatment. Expression of NK<\/jats:styled-content>1R was analysed by immunohistochemistry and for downstream pathways ((p)ERK<\/jats:styled-content>1\/2) by Western blotting in PN<\/jats:styled-content> patients and matched healthy volunteers. Effects of NK<\/jats:styled-content>1R blocking were analysed in cell cultures of primary keratinocytes by Western blotting for (p)ERK<\/jats:styled-content>1\/2 and by qPCR<\/jats:styled-content> for NK<\/jats:styled-content>1R, interleukin (IL<\/jats:styled-content>)\u20101beta, IL\u20106, IL\u20108 and TNF<\/jats:styled-content>alpha.<\/jats:p><\/jats:sec>Results<\/jats:title>Aprepitant treatment showed significant reduction in pruritus intensity (P<\/jats:italic>\u00a0<\u00a00.05) in PN<\/jats:styled-content> and relevant immunohistochemical changes (down: CD<\/jats:styled-content>5, CD<\/jats:styled-content>25, up: CD<\/jats:styled-content>79a, IL<\/jats:styled-content>4). NK<\/jats:styled-content>1R expression was higher in keratinocytes of PN<\/jats:styled-content> patients compared to healthy controls. After treatment, epidermal NK<\/jats:styled-content>1R expression increased while expression and activation of ERK<\/jats:styled-content>1\/2 decreased. In vitro<\/jats:italic>, receptor up\u2010regulation and reduced expression and activation of ERK<\/jats:styled-content>1\/2 were confirmed and reduced IL<\/jats:styled-content>\u2010expression shown when blocking NK<\/jats:styled-content>1R.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our data confirm that NK<\/jats:styled-content>1R antagonists such as aprepitant exhibit effects in the skin. Epidermal receptor expression, epidermal inflammatory ILs, ERK<\/jats:styled-content>1\/2 MAPK<\/jats:styled-content> signalling and cutaneous inflammatory infiltrate were targets of NK<\/jats:styled-content>1R antagonism. This may explain partly the antipruritic effect of NK<\/jats:styled-content>1R antagonists next to its role in the central nervous system.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.15905","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T18:03:19Z","timestamp":1566583399000},"page":"2371-2379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Neurokinin 1 receptor antagonists exhibit peripheral effects in prurigo nodularis including reduced ERK<\/scp>1\/2 activation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5601-9195","authenticated-orcid":false,"given":"K.","family":"Agelopoulos","sequence":"first","affiliation":[{"name":"Department of Dermatology and Center for Chronic Pruritus University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"R\u00fclander","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Center for Chronic Pruritus University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Dangelmaier","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Center for Chronic Pruritus University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Lotts","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Center for Chronic Pruritus University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Osada","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Center for Chronic Pruritus University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Metze","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Center for Chronic Pruritus University Hospital M\u00fcnster M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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