Short-Term Treatment with Parecoxib for Complex Regional Pain Syndrome: A Randomized, PlaceboControlled Double-Blind Trial

Abstract

Background: Complex regional pain syndrome (CRPS) is characterized by signs and symptoms of peripheral inflammation, which leads to peripheral neural sensitization associated most frequently (in about 70%) with blunt pressure hyperalgesia. Therefore, we hypothesized that treatment of CRPS patients with a selective COX-2-inhibitor would alleviate the abnormally low pressure pain threshold (PPT) and reduce pain intensity and edema. Methods: Twenty patients with CRPS type I (n = 16) and II of the upper limb and abnormally low PPT were double-blind randomised into 2 groups of 10 patients each to receive a 2-day intravenous treatment of either 80 mg parecoxib per day (group I) or placebo (NaCl 0.9%, group II). Standardized quantitative sensory testing (QST) using the DFNS protocol was performed before and after treatment. Pain intensity (NRS 0 – 10); circumferences of the fingers II, IV, and V (mm); PPT (kPa, thenar/hypothenar); and adverse events were recorded daily. Statistics: Wilcoxon-test, Mann-Whitney-U-test, Friedman-test, Fisher-test, significance level: P < 0.05. Study Design: Proof of concept trial performed in randomized, placebo-controlled, double blind style . Setting: Pain Management Center in Germany. Results: There were no group differences in PTT or other QST parameters. After treatment, PPT decreased insignificantly in group I (median [range]; before: 224.0 [121.0 – 52937] kPa, afterwards: 186.4 [101.4 – 526.5] kPa) and increased insignificantly in group II (before: 207.6 [170.0 – 320.5] kPa; afterwards: 235.4 [163.5 – 349.9] kPa). Pain scores and finger circumferences remained unchanged in both groups. Limitations: Due to difficulty in recruitment the trial was closed after inclusion of 20 patients. Conclusion: In the present proof-of-concept trial, short-term treatment with the selective COX2-inhibitor parecoxib influenced neither PPT nor edema or pain. COX-2 might be less important than previously assumed. However, the results are limited due to the small number of patients, short-term treatment, and focus on the PPT, which could have led to false negative results of the present study and covered the expected therapeutic effect. Key words: Parecoxib, complex regional pain syndrome, pressure pain threshold, pressure hyperalgesia, quantitative sensory testing, inflammation