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The ultraviolet B inflammation model: Postinflammatory hyperpigmentation and validation of a reduced UVB exposure paradigm for inducing hyperalgesia in healthy subjects
Author(s) -
Siebenga Pieter S.,
Amerongen Guido,
Klaassen Erica S.,
Kam Marieke L.,
Rissmann Robert,
Groeneveld Geert Jan
Publication year - 2019
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1353
Subject(s) - medicine , erythema , dermatology , hyperpigmentation , sensitization , inflammation , adverse effect , significant difference , gastroenterology , immunology
Abstract Background Pain models are commonly used in drug development to demonstrate analgesic activity in healthy subjects and should therefore not cause long‐term adverse effects. The ultraviolet B ( UVB ) model is a model for inflammatory pain in which three times the minimal erythema dose (3 MED ) is typically applied to induce sensitization. Based on reports of long‐lasting postinflammatory hyperpigmentation ( PIH ) associated with 3 MED , it was decided to investigate the prevalence of PIH among subjects who were previously exposed to 3 MED at our research centre. In addition, re‐evaluation of the UVB inflammation model using a reduced exposure paradigm (2 MED ) was performed in healthy subjects. Methods In the first study, all 142 subjects previously exposed to 3 MED UVB were invited for a clinical evaluation of PIH . In the second study, 18 healthy subjects were exposed to 2 MED UVB , and heat pain detection threshold ( PDT ) and PIH were evaluated. Results In total, 78 of the 142 subjects responded. The prevalence of PIH among responders was 53.8%. In the second study, we found a significant and stable difference in PDT between UVB ‐exposed and control skin 3 hr after irradiation; 13 hr post‐irradiation, the least squares mean estimate of the difference in PDT ranged from −2.6°C to −4.5°C ( p < 0.0001). Finally, the prevalence of PIH was lower in the 2 MED group compared to the 3 MED group. Conclusions The 3 MED model is associated with a relatively high prevalence of long‐lasting PIH . In contrast, 2 MED exposure produces stable hyperalgesia and has a lower risk of PIH and is therefore recommended for modelling inflammatory pain. Significance Postinflammatory hyperpigmentation is an unwanted long‐term side effect associated with the UVB inflammation model using the 3× minimal erythema dose (3 MED ) paradigm. In contrast, using a 2 MED paradigm results in hyperalgesia that is stable for 36 hr and has a lower risk of inducing postinflammatory hyperpigmentation.