cancer pain that closely model the human condition. In these models, pain severity is directly related to bone degeneration. Pain is thought to be due to tumour cells releasing cytokines and growth factors that activate T cells and osteoclasts. Osteoclast activity can be controlled by a molecule called osteoprotegerin ligand (OPGL), also known as receptor acti­vator of nuclear factor kappa- B ligand (RANKL), whose recep­tor is found on osteoclasts. Bone resorption can be blocked by a naturally secreted decoy receptor called osteoprotegerin (OPG), which binds to OPGL and prevents the activation of osteoclasts. Treatment with OPG prevents bone destruction and the secondary associated spinal cord changes and, most importantly, it significantly reduces the breakthrough pain. Bisphosphonates (e.g. zoledronic acid) are another exam­ple of drug class that could be used: they induce osteoclast apoptosis. Finally, another approach involves the use of den­osumab—a monoclonal antibody that inhibits RANKL and leads to loss of osteoclasts. All these approaches lead to some relief of pain. Bone degeneration is also associated with the release of inflammatory mediators and lowered extracellular pH that lead to the activation and sensitization of bone peri­osteum primary afferents. This is coupled with neurochemi­cal changes in the spinal cord, particularly increased glial cell activation. Glial cells are known to regulate excitatory amino acid levels and activated cells are also a source of cytokines and growth factors that will alter the surrounding neuronal microenvironment. Ultimately, all these changes lead to the induction of central sensitization, which contributes to pain maintenance.