| Popis: |
Common cancers, including breast, lung, and prostate cancers, frequently metastasize to multiple bones where they can cause significant and life-altering pain. Similar to cancer, the factors that drive bone cancer pain evolve and change with disease progression. Once cancer cells have metastasized to bone, both the cancer cells and their associated stromal cells can generate pain by releasing algogenic substances including protons, bradykinin, endothelins, prostaglandins, proteases, and tyrosine kinase activators. The release of these factors by cancer cells and their associated stromal cells can induce sensitization and activation of nerve fibers that innervate the bone. Additionally, these factors can promote a remarkable increase in the number, size, and activity of bone-destroying osteoclasts, which can ultimately result in fracture of the tumor-bearing bone. Tumor growth in bone can also generate a neuropathic pain by directly injuring nerve fibers and inducing a highly pathological sprouting of both sensory and sympathetic nerve fibers that typically innervate the bone. This structural reorganization of sensory and sympathetic nerve fibers in the bone, in conjunction with the cellular and neurochemical reorganization that occurs in the spinal cord and brain, appears to contribute to the peripheral and central sensitization that is common in advanced bone cancer pain. These mechanistic insights have begun to lead to advances in how we understand and treat bone cancer pain. |
