The mechanisms of bone pain are not easy to investigate. A patient may present with multiple osseous metastases only one of which is painful, for no obvious reason. Mechanical expansion of the periosteum and microfracture are two probable mechanisms of bone pain, but there may be multiple cytokines involved in pain modulation, such as substance P, prostaglandin E1 (PGE1) and PGE2, and bradykinin, some of which may be secreted by radiosensitive peritumoral lymphocytes. Evidence for this is indirect in that pain may diminish after only 2-4 Gy from teletherapy, before there has been significant tumor cell killing but at a time when lymphocytes exposed to these levels of radiation will die in large numbers.
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