Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.
Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.
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DOI：
10.1097/pr9.0000000000000867
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发表时间：
2021
期刊：
影响因子：
4.8
通讯作者：
Ji RR
中科院分区：
文献类型：
--
作者：
Andriessen AS;Donnelly CR;Ji RR
在这篇叙述性综述中，我们讨论了破骨细胞如何直接或间接地与疼痛感觉神经元（伤害感受器）相互作用，以促进骨癌的疼痛。许多常见的癌症，如乳腺癌、前列腺癌和肺癌，在晚期转移到骨骼，产生严重的疼痛和功能障碍。目前，目前可用于骨癌疼痛的药物疗法不足以提供安全有效的疼痛缓解。在这篇叙述性综述中，我们讨论了骨肿瘤微环境（TME）中癌细胞驱动骨癌疼痛的机制。特别是，我们强调肿瘤细胞，骨吸收破骨细胞和疼痛感觉神经元（伤害感受器），驱动骨癌疼痛之间的相互作用。我们讨论了肿瘤细胞如何在骨TME内加速破骨细胞分化（破骨细胞生成）并改变破骨细胞的活性和功能。此外，我们强调破骨细胞过度激活的这种扰动状态如何通过（1）直接机制，通过产生直接作用于感觉传入的感受性因子而导致骨癌疼痛;和（2）通过间接机制，其中破骨细胞驱动骨吸收，从而削弱荷瘤骨骼并使其容易发生骨骼相关事件，从而导致骨癌疼痛和功能障碍。最后，我们讨论了一些潜在的治疗药物，如狄诺塞单抗，双膦酸盐，和nivolumab，并讨论了它们各自对骨癌疼痛，破骨细胞过度活化，骨TME内的肿瘤生长的影响。
In this narrative review, we discuss how osteoclasts directly or indirectly interact with pain-sensing sensory neurons (nociceptors) to promote pain in bone cancer. Many common cancers such as breast, prostate, and lung cancer metastasize to bones at advanced stages, producing severe pain and functional impairment. At present, the current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. In this narrative review, we discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain. In particular, we highlight the reciprocal interactions between tumor cells, bone-resorbing osteoclasts, and pain-sensing sensory neurons (nociceptors), which drive bone cancer pain. We discuss how tumor cells present within the bone TME accelerate osteoclast differentiation (osteoclastogenesis) and alter osteoclast activity and function. Furthermore, we highlight how this perturbed state of osteoclast overactivation contributes to bone cancer pain through (1) direct mechanisms, through their production of pronociceptive factors that act directly on sensory afferents; and (2) by indirect mechanisms, wherein osteoclasts drive bone resorption that weakens tumor-bearing bones and predisposes them to skeletal-related events, thereby driving bone cancer pain and functional impairment. Finally, we discuss some potential therapeutic agents, such as denosumab, bisphosphonates, and nivolumab, and discuss their respective effects on bone cancer pain, osteoclast overactivation, and tumor growth within the bone TME.