gms | German Medical Science

Objective: Acute pain peaking 24 to 48 hours after exercise can be induced by eccentric contraction causing microtrauma induced muscle fiber destruction. Neutrophils and tissue macrophages migrate to the damaged muscle tissue, clean up the debris of broken proteins, and then initiate the regeneration phase [1]. Like all inflammatory responses, these changes are self-resolving over a period of a few days, depending upon the severity of the microtrauma. The use of NSAIDs seems a reasonable therapeutic approach to treat pain and inflammation induced by eccentric contractions. But the results of previous studies are controversial. In our hands topical ketoprofen was able to show a benefit in contrast to a low dose of oral ketoprofen [2]. One of the reasons why the effect of systemic NSAID´s might be limited is delayed recovery. Nieman et al found elevated cytokine levels in ibuprofen users following a 160 km race [3]. This study investigated the effects of 200 mg ketoprofen daily on pain induced by walking down stairs with frequent follow-ups to allow for the evaluation of recovery kinetics.

Material/Methods: This multiple-dose, double-blind, parallel-group, randomized, placebo controlled study investigated the effect of muscle pain induced by walking down stairs with a total altitude of 300–400 m depending on body weight. Subjects with a pain score of at least 3 on a 10 point categorical pain scale at 12–16 hours after exercise were randomized to placebo (n=48) and 100 mg ketoprofen b.i.d. (n=24). Intake and application of study drug occurred in the morning and evening of Day 1 to Day 6 and in the morning of Day 7.

Muscle pain was rated by the subjects using a 10 point categorical pain scale before exercise, before the first dose of study drug, at 1, 2, 4, 8, and 12 hours after the first dose of study drug. Subsequently, pain rating was performed immediately before study drug applications. The following parameters were assessed; Area under the curve of all assesments (AUC), Maximum pain (P_max), Time of maximum pain (T_max) and Time to end of pain (T_end). A Wilcoxon test for unpaired observations was used to test the null hypothesis of no difference between treatment groups against the alternative hypothesis of a difference between groups. A two-sided significance level of 5% was applied.

Results: Oral ketoprofen resulted in significantly higher pain scores (p=0.0240) compared to placebo considering the full observation period (AUC; see Table 1 [Tab. 1]). P_max and T_max were numerically higher for the ketoprofen group as compared to the placebo group but the differences were not statistically significant. Evaluation of all parameters indicated that most of the negative effect of oral ketoprofen was caused by a delay of recovery (T_end: p=0.0046).

Conclusion: In contrast to topical ketoprofen [2], systemic application of ketoprofen might cause deleterious effects on recovery from muscle soreness induced by eccentric contraction. Since systemic application of ibuprofen and celecoxib showed reduced muscle soreness without effects on recovery [4], [5], the effect might be drug specific or may depend on mode and timing of drug application.