| [ Summary ] |
Bone pain is one of the most frequent complications associated with cancer metastasis to the bones and is a major cause of increased morbidity and mortality. The precise mechanisms related to bone pain are still poorly understood. However, clinical observations that the inhibitors of osteoclastic bone resorption, with distinct mechanisms of action, significantly reduce bone pain strongly suggest that osteoclasts play a critical role in causing bone pain. The acid-sensing receptors expressed on nociceptive sensory neurons innervating bone tissue are activated by protons released from bone-resorbing osteoclasts, followed by propagation of intracellular signaling pathways in sensory neuronal cells, leading to transduction of bone pain signals to the brain. These results suggest that inhibition of these events would be a mechanism-based intervention for the treatment of cancerinduced bone pain. |