Department of Anesthesiology, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, China.
Pain Med. 2017 Dec 1;18(12):2433-2442. doi: 10.1093/pm/pnx004.
This study explored the putative mechanisms of miRNAs in the anterior cingulate cortex (ACC) in modulation of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve.
MiRNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine miRNA expression profile in the ACC after CCI of the sciatic nerve. MiRNA mimics were then used to examine the role of miR-539 in the ACC in modulation of NR2B subunit expression and neuropathic pain in rats.
The expression of nine miRNAs was enhanced, and the expression of 12 miRNAs, such as miR-539, was reduced in the ACC after CCI. We confirmed that miR-539 expression was decreased robustly in the contralateral, but mildly in the ipsilateral, ACC. This was associated with enhanced protein levels of NR2B in a similar pattern. Furthermore, administrations of miR-539 mimics into the contralateral ACC, but not the ipsilateral ACC, attenuated CCI-induced mechanical allodynia. This was associated with reduction in protein levels of NR2B in the contralateral ACC. Finally, administrations of Ro25-6981 into the contralateral ACC attenuated the CCI-induced mechanical allodynia to a greater extent than the ipsilateral ACC.
Our results suggested that CCI induces lateralized adaptations of NR2B subunit expression in the ACC, which is likely in part contributed by alterations of miR-539 expression, and may promote the regulations of neuropathic pain via NR2B-containing NMDA receptor-mediated neuronal mechanisms.
本研究探讨了前扣带皮层（ACC）中 microRNAs（miRNAs）在慢性坐骨神经缩窄损伤（CCI）诱导的神经性疼痛调节中的潜在机制。
采用 miRNA 微阵列和实时定量聚合酶链反应（qRT-PCR）检测 CCI 后 ACC 中的 miRNA 表达谱。然后使用 miRNA 模拟物来研究 miR-539 在 ACC 中对 NR2B 亚基表达和大鼠神经性疼痛的调节作用。
CCI 后，ACC 中 9 种 miRNA 的表达增强，12 种 miRNA（如 miR-539）的表达降低。我们证实 miR-539 在对侧 ACC 中表达显著降低，但在同侧 ACC 中轻度降低。这与 NR2B 蛋白水平的增强模式相似。此外，将 miR-539 模拟物注入对侧 ACC，但不是同侧 ACC，可减轻 CCI 诱导的机械性痛觉过敏。这与对侧 ACC 中 NR2B 蛋白水平的降低有关。最后，将 Ro25-6981 注入对侧 ACC 可减轻 CCI 诱导的机械性痛觉过敏，程度大于同侧 ACC。
我们的结果表明，CCI 诱导 ACC 中 NR2B 亚基表达的偏侧适应，部分可能由 miR-539 表达的改变引起，并可能通过 NR2B 含有 NMDA 受体的神经元机制调节神经性疼痛。
