Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, LSN 560, PO Box 245050, Tucson, AZ 85724, USA.
Pain. 2013 Dec;154 Suppl 1:S54-S62. doi: 10.1016/j.pain.2013.07.044. Epub 2013 Jul 31.
Common cancers, including cancers of the breast, lung, and prostate, frequently metastasize to multiple bones where they can cause significant and life-altering pain. Similar to cancer itself, 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 generate pain by releasing algogenic substances including protons, bradykinin, endothelins, prostaglandins, proteases, and tyrosine kinase activators. The release of these factors by cancer/stromal cells can induce sensitization and activation of nerve fibers that innervate the bone. Additionally, these factors can drive 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 as well as inducing an active and highly pathological sprouting of both sensory and sympathetic nerve fibers that normally innervate the bone. This structural reorganization of sensory and sympathetic nerve fibers in the bone, combined 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 both how we understand and treat bone cancer pain.
常见的癌症，包括乳腺癌、肺癌和前列腺癌，经常转移到多个骨骼，在那里它们会引起严重的、改变生活的疼痛。与癌症本身类似，导致骨癌疼痛的因素随着疾病的进展而演变和变化。一旦癌细胞转移到骨骼，癌细胞及其相关基质细胞都会通过释放致痛物质（包括质子、缓激肽、内皮素、前列腺素、蛋白酶和酪氨酸激酶激活剂）引起疼痛。这些因子的释放可以诱导支配骨骼的神经纤维的敏化和激活。此外，这些因子可以驱动破骨细胞数量、大小和活性的显著增加，最终导致肿瘤骨骨折。肿瘤在骨骼中的生长也可以通过直接损伤神经纤维以及诱导正常支配骨骼的感觉和交感神经纤维的活跃和高度病理性的发芽来产生神经性疼痛。骨骼中感觉和交感神经纤维的这种结构重组，加上脊髓和大脑中发生的细胞和神经化学重组，似乎有助于晚期骨癌疼痛中常见的外周和中枢敏化。这些机制上的见解已经开始推动我们对骨癌疼痛的理解和治疗的进展。
