A simple pain model for the evaluation of analgesic effects of NSAIDs in healthy subjects


Leopold Schmetterer PhD, Department of Clinical Pharmacology, Währinger Gürtel 18–20, A-1090 Vienna, Austria. Tel.: + 43 14 0400 2981; Fax: + 43 14 0400 2998; E-mail: leopold.schmetterer@univie.ac.at


Aims  Non-steroidal anti-inflammatory drugs (NSAIDs) are believed to counteract inflammation and inflammation-induced sensitization of nociceptors by inhibiting peripheral prostaglandin synthesis. We evaluated an experimental pain model for NSAIDs, that included an inflammatory component to mimic clinical inflammatory pain conditions.

Methods  The study was performed in a randomized, double-blind, placebo-controlled, two-way crossover design on 32 healthy volunteers. A small skin area of the proximal upper leg was irradiated with a UVB source using three times the individually estimated minimal erythema dose. Twenty hours after irradiation skin temperature, heat pain threshold and tolerance in sunburn spot were measured using a thermal sensory testing. These measurements were repeated 2 h after medication of either 800 mg ibuprofen as single oral dose or placebo capsules. Effects of ibuprofen on outcome parameters were assessed with analyses of covariance (ancova).

Results  Placebo did not affect heat pain threshold or tolerance. By contrast, ibuprofen increased heat pain threshold by 1.092 °C [confidence interval (CI) 0.498, 1.695; P = 0.0008) compared with placebo. Heat pain tolerance also increased significantly by 1.618 °C (CI 1.062, 2.175; P = 0.0001).

Conclusion  The pain model we evaluated was well tolerated in all subjects and the effects of ibuprofen were highly significant. This model is simple, sensitive to NSAIDs’ effects and therefore has potential for future experimental pain studies.