Department of Anesthesiology, Women's and Children's Hospital Affiliated to Qingdao University, 6 Tongfu Road, Qingdao, Shandong 266034, China.
Department of Orthopedics, The Affiliated Hospital of Qingdao University, 59 Hai Er Road, Qingdao, Shandong 266061, China.
Tissue Cell. 2021 Feb;68:101438. doi: 10.1016/j.tice.2020.101438. Epub 2020 Oct 23.
Cancer pain, especially bone cancer pain, is a pain state often caused by inflammation or dysfunctional nerves. Moreover, in the management of cancer pain, opioid especially morphine is widely used, however, it also brings severe side effects such as morphine tolerance to the patient (Deandrea et al., 2008). A growing body of literatures demonstrated that neuroinflammation is mediated by microglia. As the macrophages like immune cells, microglia play an important role in the pathogenesis of cancer pain and morphine tolerance. Microglia acquire different activation states to regulate the function of these cells. As to M1 phenotype, microglia release pro-inflammatory cytokines and neurotoxic molecules that promote inflammation and cytotoxic reactions. Conversely, when microglia represent M2 phenotypes secreting anti-inflammatory cytokines and nutrient factors that promote the function of repair, regeneration and restore homeostasis. A better understanding of microglia activation in cancer pain and morphine tolerance is crucial for the development of hypothesized neuroprotective drugs. Targeting microglia different polarization states by the inhibition of their deleterious pro-inflammatory neurotoxicity and/or enhancing their beneficial anti-inflammatory protective function seems to be an effective treatment for cancer pain and morphine tolerance.
癌症疼痛，尤其是骨癌疼痛，是一种常由炎症或功能失调的神经引起的疼痛状态。此外，在癌症疼痛的管理中，阿片类药物，尤其是吗啡，被广泛应用，但它也给患者带来了严重的副作用，如吗啡耐受（Deandrea 等人，2008）。越来越多的文献表明，神经炎症是由小胶质细胞介导的。作为类似巨噬细胞的免疫细胞，小胶质细胞在癌症疼痛和吗啡耐受的发病机制中发挥重要作用。小胶质细胞获得不同的激活状态来调节这些细胞的功能。对于 M1 表型，小胶质细胞释放促炎细胞因子和神经毒性分子，促进炎症和细胞毒性反应。相反，当小胶质细胞表现出 M2 表型时，它们会分泌抗炎细胞因子和营养因子，促进修复、再生和恢复体内平衡的功能。更好地了解小胶质细胞在癌症疼痛和吗啡耐受中的激活对于开发假设性的神经保护药物至关重要。通过抑制其有害的促炎神经毒性和/或增强其有益的抗炎保护功能来靶向小胶质细胞的不同极化状态，似乎是治疗癌症疼痛和吗啡耐受的有效方法。
