INFLAMMATORY MODELS OF CUTANEOUS HYPERALGESIA ARE SENSITIVE TO EFFECTS OF IBUPROFEN IN MAN

A new experimental procedure was developed to quantify the analgesic a ctions of non-steroidal anti-inflammatory drugs (NSAIDs) in healthy hu man subjects. In order to mimic the clinical situation, the drug was ' therapeutically' administered 1 day after induction of inflammation by freezing a small skin area. The procedure was easily tolerated and le d to a marked hyperalgesia without ongoing pain which was tested using mechanical impact stimulation and magnitude estimation. For compariso n, we used a previously established model of repeated noxious pinching of an interdigital skin web which induces a hyperalgesia to pressure (rated via visual analogue scale), and topical application of capsaici n which leads to quantifiable flare and allodynia responses. The effec ts of a cumulative drug regime of ibuprofen in 2 different doses (3 x 400 mg and 3 x 800 mg at 2-h intervals) were tested versus placebo usi ng a double-blind cross-over design with 24 volunteers of either gende r. Ibuprofen caused a significant suppression of the hyperalgesia to r epeated pinching and of the hyperalgesia to impact stimulation followi ng freeze trauma. In contrast, there was no effect on the areas of fla re and allodynia induced by capsaicin application and on the impact ev oked sensations from untreated skin. The two dosages of ibuprofen, how ever, appeared to be equally effective in a way that suggests a platea uing of the antihyperalgesic effect. The two models in which hyperalge sia is affected by ibuprofen, i.e., repeated pinching and impact stimu lation after freeze trauma, seem to provide comparable sensitivity. Th e freeze model may in the future have the advantage to allow for a bet ter temporal resolution of the drug's action profile.