Difference of pain vulnerability in adult and juvenile rodents: the role of SIRT1-mediated ClC-3 trafficking in sensory neurons.
Difference of pain vulnerability in adult and juvenile rodents: the role of SIRT1-mediated ClC-3 trafficking in sensory neurons.
复制标题
DOI：
10.1097/j.pain.0000000000002176
复制
发表时间：
2021-01
期刊：
影响因子：
7.4
通讯作者：
Xiao-Long Zhang;Jin-Jun Zhang;Zi-Hang Chen;Kai-bin Yang;Xi Zhang;Yi-bin Xiao;Y. Lei;Xian-Ying C
中科院分区：
文献类型：
--
作者：
Xiao-Long Zhang;Jin-Jun Zhang;Zi-Hang Chen;Kai-bin Yang;Xi Zhang;Yi-bin Xiao;Y. Lei;Xian-Ying C
摘要成年人比未成年人更容易遭受慢性疼痛，其潜在机制尚不清楚。SIRT 1作为一种重要的衰老相关蛋白，具有延长寿命的功能，SIRT 1是否在成人和青少年不同的疼痛易感性中发挥作用尚不清楚。在此，我们发现SIRT 1在背根神经节（DRG）的表达水平与疼痛易感性有关。神经损伤后，SIRT 1在成年啮齿动物DRG中的表达降低，而在幼年啮齿动物DRG中的表达增加。SIRT 1的差异性操作消除了成年和幼年啮齿动物之间的不同疼痛脆弱性。SIRT 1还与ClC-3通道相互作用，介导DRG神经元ClC-3膜运输和Cl？电流。ClC-3的差异操作也消除了成年和青少年啮齿动物之间的疼痛脆弱性的差异。抗炎能力的不同决定了SIRT 1和ClC-3运输的不同变化趋势，导致成年和幼年啮齿动物不同的疼痛易感性。此外，血清SIRT 1水平与慢性疼痛患者的疼痛评分呈负相关。这些发现揭示了成年和幼年啮齿动物疼痛易感性差异的机制，并为慢性疼痛的年龄特异性治疗提供了证据。
ABSTRACT Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 as important aging-related protein with function of lifespan extension, whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. Following nerve injury, the expression of SIRT1 in DRG was decreased in adult rodents while increased in juvenile rodents. Differential manipulation of SIRT1 abolished the different pain vulnerability between adult and juvenile rodents. Furthermore, SIRT1 interacted with ClC-3 channel and mediated ClC-3 membrane trafficking and Cl¯ current in DRG neurons. Differential manipulation of ClC-3 also abolished the difference in pain vulnerability between adult and juvenile rodents. The different anti-inflammatory ability determined the different change trends of SIRT1 and ClC-3 trafficking contributed to the different pain vulnerability in adult and juvenile rodents. In addition, the serum SIRT1 level was negatively correlated with pain score in chronic pain patients. These findings revealed the mechanism of the difference in pain vulnerability between adult and juvenile rodents and provided evidence for age-specific treatment of chronic pain.