中文摘要：

近十年来,我们实验室从局部肿瘤细胞产生甲醛的角度（相对于环境中的甲醛污染物,我们称之为内源性甲醛）,探讨转移性骨癌痛的新机制。在转移性骨癌痛模型中,侵润入骨髓中的肿瘤细胞,通过丝氨酸羟甲基转移酶1（serine hydroxymethyltransferase 1,SHMT1）、SHMT2及赖氨酸特异性组蛋白去甲基化酶1（lysine-specific histone demethylase 1,LSD1）的催化产生甲醛。此内源性甲醛能激活伤害性感觉神经纤维上的辣椒素受体（transient receptor potential vanilloid subfamily member 1,TRPV1）,导致骨癌痛;另一方面,在癌细胞骨转移的情形下,骨质破坏增加的同时激活了成骨细胞,这些激活的成骨细胞释放出I型胰岛素样生长因子（insulin-like growth factor-I,IGF-I）,后者通过其受体介导的信号传导通路,上调外周神经纤维上的TRPV1受体。这样,升高的内源性甲醛激活TRPV1受体,导致转移性骨癌痛的发生。这为我们深入理解转移性骨癌痛的机制以及潜在的临床干预措施,提供了一个新视角。

英文摘要：

In the past ten years, the serial investigations in our group focused on the role of cancer cellsderived endogenous formaldehyde in bone cancer pain. We found that cancer cells produced formaldehyde through demethylation by serine hydroxymethyltransferase（SHMT1 and SHMT2） and lysine-specific histone demethylase 1（LSD1）. When the cancer cells metastasized into bone marrow, the elevated endogenous formaldehyde induced bone cancer pain through activation on the transient receptor potential vanilloid subfamily member 1（TRPV1） in the peripheral nerve fibers. More interestingly, TRPV1 expressions in the peripheral fibers were up-regulated by the local insulin-like growth factor I（IGF-I） produced by the activated osteoblasts. In conclusion, tumor tissue-derived endogenous formaldehyde induced bone cancer pain via TRPV1 activation.Key words Bone cancer pain; Formaldehyde; Transient receptor potential vanilloid subfamily member 1（TRPV1）; Insulin-like growth factor I（IGF-I）