Involvement of macrophages and spinal microglia in osteoarthritis pain

Purpose of Review: Chronic pain in osteoarthritis (OA) is characterized by pain sensitization, which involves both peripheral andcentral mechanisms. Studies suggest synovial macrophage and spinal microglia are implicated in pain sensitization in OA. We,therefore, reviewed the evidence of whether synovial macrophage and spinal microglia facilitated pain sensitization at diverselevels and how this event occurred in OA.Recent Findings: Peripherally, joint inflammation is now believed to be a source of OA-related pain. Synovial macrophagesaccumulate in OA inflamed synovium and display a pro-inflammatory phenotype. Abundant macrophage-derived pro-inflammatory cytokines and other pain-causing substance facilitate hyperexcitation of primary sensory neuron in OA-related pain.Thus, activated synovial macrophage was considered a predictor for phenotyping of OA pain clinically. In response to affectedjoint-derived strong nociception, aberrant neuronal excitability is often associated with the hyperactivity of microglia in the spinaldorsal horn, thereby leading to central sensitization.Summary: Hyperactivity of synovial macrophage and spinal microglia underlies the mechanisms of pain sensitization at theperipheral and central level in OA. This concept provides not only a clinically relevant strategy for identifying the phenotype ofOA-related pain but also has the potential to develop individualized interventions for OA, particularly in those patients withhyperactivity of macrophage and microglia