Microglia are involved in induction of chronic pain. In knee osteoarthritis (OA), spinal microglia are activated, but the involvement of brain microglia remains unclear. Therefore, we examined the role of brain microglia in mechanical hypersensitivity in OA.
　The OA model was prepared by administration of monoiodoacetate (MIA) into the left knee joint cavity of ddY male mice . Brain slices prepared after MIA administration were stained with an anti-ionized calcium binding molecular 1 (Iba1) antibody, a marker of microglia. Pain thresholds were measured using von Frey filaments. Cartilage damage was evaluated by Safranin O staining.
　Activation of microglia in the hippocampus was observed from 4 weeks after MIA administration, peaking at 6 weeks and continuing thereafter. The decreased pain threshold and knee joint damage were observed continuously from 2 weeks after MIA administration. Furthermore, at 5 weeks after MIA administration, local administration of clodronate liposome, which deplete microglia, significantly prevented the decreased pain threshold. These results indicate that there is temporal lag between knee joint damage and pain and activation of hippocampal microglia in the OA model mice, and that these cells are involved in persistent pain.