title: Placebo controlled, crossover validation study of oral ibuprofen and topical hydrocortisone- 21-acetate for a model of ultraviolet B radiation (UVR)-induced pain and inflammation.
abstract: BACKGROUND
  Pain related to ultraviolet B radiation (UVR) induced sunburn is an established, simple, acute pain model. One of the major criticisms is related to the potential dermal adverse events caused by the UVR exposure. This study tried to validate the model for oral and topical drugs and to define the minimum required UVR exposure.
  
  
  METHODS
  This subject- and observer-blinded, placebo-controlled, crossover study evaluated 600 mg oral ibuprofen (IB) and topical hydrocortisone-21-acetate (HC) twice daily (bid) in 24 healthy volunteers. Treatment started immediately after irradiation and again at 12 hours, 24 hours, and 36 hours post-UVR. Assessment of hyperalgesia to heat and signs of inflammation (erythema, skin temperature) for all areas was performed after UVR and again at 6, 12, 24, 36, and 48 hours. Subjects returned within 4-11 days to the study site for the second period of the study. As in the first period, subjects received HC at one side and topical placebo on the other side, but oral treatment was crossed-over.
  
  
  RESULTS
  The primary analysis failed to show the expected superiority of the IB-group vs the placebo group in period 1 of the study. Evaluating period 2 alone clearly showed the expected treatment effects of IB for erythema and heat pain threshold. The results were less pronounced for skin temperature. In contrast to IB vs oral placebo, there were no differences in treatment response between HC and topical placebo. UVR at all dosages induced profound erythema and reduction of heat pain threshold without causing blisters or other unexpected discomfort to the subjects. The changes were almost linear between 1 and 2 minimal erythema doses (MED), whereas the change from 2 to 3 MED was less pronounced.
  
  
  CONCLUSIONS
  Use of 2 MED in upcoming studies seems to be reasonable to limit subjects' UVB exposure. The following procedural changes are suggested: Intensified training sessions before randomization to treatmentIncrease in sample size if they are crossover studiesSimplification in design (either oral or topical treatment).
authors.affiliation: Department of Clinical Operations, X-pert Med GmbH, Graefelfing, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rother
authors.forename: Ilka
authors.initials: I
authors.lastname: Rother
references.citation: Arch Dermatol. 2008 May;144(5):620-4
references.pmid: 18490588
references.citation: Cutis. 2000 Jul;66(1):53-8
references.pmid: 10916693
references.citation: J Invest Dermatol. 2004 Jan;122(1):183-9
references.pmid: 14962107
references.citation: Br J Anaesth. 1993 Aug;71(2):201-5
references.pmid: 8123392
references.citation: Biometrics. 1972 Jun;28(2):577-84
references.pmid: 4556704
references.citation: J Am Acad Dermatol. 1981 Oct;5(4):411-22
references.pmid: 7287956
references.citation: Arch Dermatol. 1988 Jun;124(6):869-71
references.pmid: 3377516
references.citation: Skin Pharmacol Physiol. 2005 Sep-Oct;18(5):234-40
references.pmid: 16015022
references.citation: Br J Clin Pharmacol. 2003 Aug;56(2):165-72
references.pmid: 12895189
references.citation: Pain. 1996 Oct;67(2-3):327-33
references.pmid: 8951926
references.citation: J Invest Dermatol. 1993 Jan;100(1):35S-41S
references.pmid: 8423392
references.citation: Clin Exp Dermatol. 2002 Jun;27(4):314-8
references.pmid: 12139679
references.citation: Pain. 1998 Jun;76(3):317-325
references.pmid: 9718250