Nuclear factor kappa B regulated monocyte chemoattractant protein-1/chemokine CC motif receptor-2 expressing in spinal cord contributes to the maintenance of cancer-induced bone pain in rats:

Background: Chemokine, monocyte chemoattractant protein-1 (MCP-1), is a potential factor to cause cancer-induced bone pain (CIBP). NF-kB signaling is very important in mediating the expression of chemokines and may have a role in CIBP. However, the mechanism is still unclear. The present study investigates the role of NF-kB in CIBP by regulating MCP-1/chemokine CC motif receptor 2 (CCR2) signaling pathway. Methods: A rat CIBP model was established by injecting Walker 256 cells into the femur medullary cavity. Nine days later, animals were intrathecally administrated with MCP-1 neutralizing antibody, CCR2 antagonist (RS504293) or NF-кB inhibitor (BAY11-7081). Mechanical paw withdrawal threshold was used to assess pain behavior and sciatic functional index and radiographic images were adopted to evaluate the damage of nerve and bone. The spinal cords were harvested for Western blot and qRT-PCR. The distribution of MCP-1, CCR2, and NF-кB were detected by double immunofluorescent staining. Results: CIBP cause...