PPAR–Gamma Agonists Inhibit Carrageenan–Induced Inflammatory Pain in Rats

Objectives: Peroxisome proliferator–activated receptor gamma (PPAR–gamma) is known to be involved in an anti–inflammatory pathway through the cyclooxygenase (COX) cascade. We previously demonstrated that locally injected dexmedetomidine has an inhibitory effect on acute inflammatory pain in rats and its anti–inflammatory effect occurs via PPAR–gamma using mouse macrophage–like cells. We hypothesized that PPAR–gamma agonists have an inhibitory effect on acute inflammatory pain. Therefore, we evaluated the effect of locally administered PPAR–gamma agonists, 15–deoxy–delta–12,14–prostaglandin J2 (15d–PGJ2) and thiazolidine, on acute inflammatory pain in rats.
Methods: After obtaining approval from the Animal Care and Use Committee of our institute, we studied male Sprague–Dawley rats. Acute inflammatory pain was induced by an intraplantar injection of 0.2% carrageenan into the hindpaws of rats. PPAR–gamma agonist (15d–PGJ2 or thiazolidine) at 10 µM was combined with carrageenan and injected into the hindpaws. In order to evaluate the effects of PPAR–gamma agonists on pain, the paw–withdrawal threshold on applying mechanical stimulation with von Frey filaments was measured until 6 hours after injection of control (saline), carrageenan alone, or carrageenan + PPAR–gamma agonist (15d–PGJ2 or thiazolidine). The differences in the withdrawal threshold at each time point after injection and area under the withdrawal threshold time–curve (AUC) among test solutions were analyzed using analysis of variance (ANOVA).
Results: The paw–withdrawal threshold decreased after the injection of carrageenan alone into the hindpaws. The paw–withdrawal thresholds and AUC in the rats injected with carrageenan + PPAR–gamma agonist were significantly larger than that in the rats injected with carrageenan alone.
Conclusions: The results indicate that PPAR–gamma agonists had an inhibitory effect on carrageenan–induced inflammatory pain. The finding suggests that PPAR–gamma agonists may be useful as a locally administered anti–inflammatory drug.