Complex regional pain syndrome (CRPS) is a debilitating chronic pain disorder with no effective treatments. Growing evidence implicates aberrant immune regulation in the skin and T cell dysfunction in CRPS pathology. MicroRNA (miRNA) show promise in identifying biomarkers and disease mechanisms. miRNA cluster miR-106b-25 is dysregulated in CRPS patient whole blood and serum derived small extracellular vesicles (sEVs) compared to healthy controls. miR-106b-25 members are predicted to target several immune genes related to T cell function including CD69. We hypothesize that miR-106b-25 cluster plays a role in T-cell dysfunction by regulating members of CD69 signaling pathway. Here we examine miR-106b-25 mediated signaling in sEVs, whole blood, and skin from the tibia fracture model (TFM) of CRPS.