Chemokines and Lipid Mediators Modulate the Resolution of Inflammatory Arthritis Pain

Pain is a persistent feature of rheumatoid arthritis and sensory neuron-macrophage crosstalk in the dorsal root ganglia (DRG) plays a fundamental role for the establishment and maintenance of RA pain. In the K/BxN serum-transfer model of inflammatory arthritis, we observed that hind paw hypersensitivity (allodynia) persists after joint swelling is resolved. This phase is associated with the presence of CX3CR1-macrophages into the DRG and an imbalance in lipid mediators. Specifically, we found no difference in prostaglandins PGD2 and PGE2 levels, but a significant decrease in the pro-resolving lipid mediator Maresin1 (MaR1). The administration of MaR1 reversed K/BxN serum-transfer allodynia and this effect was maintained for 2 weeks after the last administration. Analysis of leukocytes in the DRG revealed that MaR1 treatment was associated with lower numbers of pro-inflammatory macrophages. Altogether these observations suggest that MaR1 treatment attenuates allodynia in inflammatory arthritis and reduces macrophage infiltration. I will discuss the proposal that inflammatory pain and pain that persists when inflammation is resolving may be reliant on partially distinct mechanisms, both involving monocytes/macrophages and biosynthesis of lipid mediators. CX3CR1-mediated mechanisms and lipid mediator biosynthesis facilitate such crosstalk and may constitute novel targets for the resolution of RA pain.