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Eur J Pain. 2018 Dec 29. doi: 10.1002/ejp.1353. [Epub ahead of print]

The ultraviolet B inflammation model: Postinflammatory hyperpigmentation and validation of a reduced UVB exposure paradigm for inducing hyperalgesia in healthy subjects.

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Centre for Human Drug Research, Leiden, The Netherlands.
Leiden University Medical Centre, Leiden, The Netherlands.
Leiden Academic Centre for Drug Research, Leiden, The Netherlands.



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 (3MED) is typically applied to induce sensitization. Based on reports of long-lasting postinflammatory hyperpigmentation (PIH) associated with 3MED, it was decided to investigate the prevalence of PIH among subjects who were previously exposed to 3MED at our research centre. In addition, re-evaluation of the UVB inflammation model using a reduced exposure paradigm (2MED) was performed in healthy subjects.


In the first study, all 142 subjects previously exposed to 3MED UVB were invited for a clinical evaluation of PIH. In the second study, 18 healthy subjects were exposed to 2MED UVB, and heat pain detection threshold (PDT) and PIH were evaluated.


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 2MED group compared to the 3MED group.


The 3MED model is associated with a relatively high prevalence of long-lasting PIH. In contrast, 2MED exposure produces stable hyperalgesia and has a lower risk of PIH and is therefore recommended for modelling inflammatory pain.


Postinflammatory hyperpigmentation is an unwanted long-term side effect associated with the UVB inflammation model using the 3× minimal erythema dose (3MED) paradigm. In contrast, using a 2MED paradigm results in hyperalgesia that is stable for 36 hr and has a lower risk of inducing postinflammatory hyperpigmentation.


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