SPM limits inflammation in SCD in mice, which has implications for pain control. (A) SCD is characterized by heighted inflammation involving leukocytes, platelets, and endothelial cells. Sickle RBCs can obstruct the vasculature, which can lead to organ damage and pain. (B) 17R-RvD1 decreases inflammation, reactive oxygen species (ROS), vaso-occlusion, and, ultimately, tissue damage. Inflammatory cytokines, and mediators like prostaglandins (which are elevated in SCD) are directly linked to pain. High levels of proinflammatory cytokines like interleukin 6 (IL-6) activate nociceptors to initiate pain. Importantly, 17R-RvD1 decreases NF-κB activation and IL-6 in SCD mice, which implies a mechanistic link for decreasing pain in SCD. PMN, polymorphonuclear neutrophil.