Prostaglandin D2-glycerol ester decreases carrageenan-induced inflammation and hyperalgesia in mice.

Pain is one of the cardinal signs of inflammation and is present in many inflammatory conditions. Therefore, anti-inflammatory drugs such as NSAIDs also have analgesic properties. We previously showed that prostaglandin D₂-glycerol ester (PGD₂-G), endogenously produced by cyclooxygenase-2 from the endocannabinoid 2-arachidonoylglycerol, has anti-inflammatory effects in vitro and in vivo that are partly mediated by DP1 receptor activation. In this work, we investigated its effect in a model of carrageenan-induced inflammatory pain. PGD₂-G decreased hyperalgesia and edema, leading to a faster recovery. Moreover, PGD₂-G decreased carrageenan-induced inflammatory markers in the paw as well as inflammatory cell recruitment. The effects of PGD₂-G were independent from metabolite formation (PGD₂ and 15d-PGJ₂-G) or DP1 receptor activation in this model. Indeed PGD₂ delayed recovery from hyperalgesia while 15d-PGJ₂-G worsened the edema. However, while PGD₂-G decreased hyperalgesia in this model of inflammatory pain, it had no effect when tested in the capsaicin-induced pain model. While the targets mediating the effects of this bioactive lipid in inflammatory pain remain to be elucidated, our findings further support the interest of anti-inflammatory lipid mediators in the management of inflammatory pain.