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

Abstract

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 degrees C [confidence interval (CI) 0.498, 1.695; P = 0.0008) compared with placebo. Heat pain tolerance also increased significantly by 1.618 degrees 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.

Figure 1

Overall subject disposition.

Figure 2

Effects of 800 mg ibuprofen (▴) or placebo (▿) on heat pain threshold 2 h after oral intake separated for session 1 and session 2. Results are presented as means ± SD.

Figure 3

Effects of 800 mg ibuprofen (▴) or placebo (▿) on heat pain tolerance 2 h after oral intake separated for session 1 and session 2. Results are presented as means ± SD.

Figure 4

Effects of 800 mg ibuprofen (▴) or placebo (▵, ▿) on skin temperature differences between normal skin and phototoxic erythema 2 h after oral intake separated for session 1 and session 2. Up triangles (▵) represent means of male subjects, down triangles (▿) represent means of female subjects. Results are presented as means ± SD.