{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:14:24Z","timestamp":1781795664968,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Centre for Human Drug Research"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2019,5]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Pain models are commonly used in drug development to demonstrate analgesic activity in healthy subjects and should therefore not cause long\u2010term adverse effects. The ultraviolet B (UVB<\/jats:styled-content>) model is a model for inflammatory pain in which three times the minimal erythema dose (3MED<\/jats:styled-content>) is typically applied to induce sensitization. Based on reports of long\u2010lasting postinflammatory hyperpigmentation (PIH<\/jats:styled-content>) associated with 3MED<\/jats:styled-content>, it was decided to investigate the prevalence of PIH<\/jats:styled-content> among subjects who were previously exposed to 3MED<\/jats:styled-content> at our research centre. In addition, re\u2010evaluation of the UVB<\/jats:styled-content> inflammation model using a reduced exposure paradigm (2MED<\/jats:styled-content>) was performed in healthy subjects.<\/jats:p><\/jats:sec>Methods<\/jats:title>In the first study, all 142 subjects previously exposed to 3MED UVB<\/jats:styled-content> were invited for a clinical evaluation of PIH<\/jats:styled-content>. In the second study, 18 healthy subjects were exposed to 2MED UVB<\/jats:styled-content>, and heat pain detection threshold (PDT<\/jats:styled-content>) and PIH<\/jats:styled-content> were evaluated.<\/jats:p><\/jats:sec>Results<\/jats:title>In total, 78 of the 142 subjects responded. The prevalence of PIH<\/jats:styled-content> among responders was 53.8%. In the second study, we found a significant and stable difference in PDT<\/jats:styled-content> between UVB<\/jats:styled-content>\u2010exposed and control skin 3\u00a0hr after irradiation; 13\u00a0hr post\u2010irradiation, the least squares mean estimate of the difference in PDT<\/jats:styled-content> ranged from \u22122.6\u00b0C to \u22124.5\u00b0C (p\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.0001). Finally, the prevalence of PIH<\/jats:styled-content> was lower in the 2MED<\/jats:styled-content> group compared to the 3MED<\/jats:styled-content> group.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The 3MED<\/jats:styled-content> model is associated with a relatively high prevalence of long\u2010lasting PIH<\/jats:styled-content>. In contrast, 2MED<\/jats:styled-content> exposure produces stable hyperalgesia and has a lower risk of PIH<\/jats:styled-content> and is therefore recommended for modelling inflammatory pain.<\/jats:p><\/jats:sec>Significance<\/jats:title>Postinflammatory hyperpigmentation is an unwanted long\u2010term side effect associated with the UVB<\/jats:styled-content> inflammation model using the 3\u00d7 minimal erythema dose (3MED<\/jats:styled-content>) paradigm. In contrast, using a 2MED<\/jats:styled-content> paradigm results in hyperalgesia that is stable for 36\u00a0hr and has a lower risk of inducing postinflammatory hyperpigmentation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1353","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T22:17:51Z","timestamp":1546294671000},"page":"874-883","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The ultraviolet B inflammation model: Postinflammatory hyperpigmentation and validation of a reduced UVB<\/scp> exposure paradigm for inducing hyperalgesia in healthy subjects"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-9454","authenticated-orcid":false,"given":"Pieter S.","family":"Siebenga","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"van Amerongen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica S.","family":"Klaassen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke L.","family":"de Kam","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Rissmann","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"},{"name":"Leiden University Medical Centre Leiden The Netherlands"},{"name":"Leiden Academic Centre for Drug Research Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert Jan","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden The Netherlands"},{"name":"Leiden University Medical Centre Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"387","article-title":"Common dermatologic disorders in skin of color: A comparative practice survey","volume":"80","author":"Alexis A. 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