Pain is the major debilitating symptom of osteoarthritis (OA), which is difficult to treat. In OA patients joint tissue damage only poorly associates with pain, indicating other mechanisms contribute to OA pain. Immune cells regulate the sensory system, but little is known about their involvement in OA pain. Here we report that macrophages accumulate in the dorsal root ganglia (DRG) distant from the site of injury in two rodent models of OA. DRG macrophages acquired a M1-like phenotype and depletion of DRG macrophages resolved OA pain in male and female mice. Sensory neurons innervating the damaged knee joint shape DRG macrophages into a M1-like phenotype. Persisting OA pain, accumulation of DRG macrophages, and their programming into M1-like phenotype was independent of Nav1.8 nociceptors. Inhibition of M1-like macrophages in the DRG, by intrathecal injection of a IL4-IL10 fusion protein or M2-like macrophages resolved persistent OA pain. In conclusion, these findings reveal a crucial role for macrophages...