Li Guangling, Lu Xianfu, Zhang Suming, Zhou Qiangqiang, Zhang Licai
Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
Neurochem Res. 2015 May;40(5):1053-62. doi: 10.1007/s11064-015-1564-7. Epub 2015 Apr 7.
The cerebrospinal fluid-contacting nucleus (CSF-CN) has been demonstrated to be involved in neuropathic pain, but the underlying molecular mechanisms remain unclear. Previous work has shown that mTOR and ERK1/2 are important signaling pathways regulating neuropathic pain. However, studies on the interactions between these major pathways in neuropathic pain are very rare. Therefore, the purpose of this study is to determine whether mTOR and ERK1/2 exist in the CSF-CN and elucidate their alterations in neuropathic pain, especially, the crosstalk between them. Our results showed that mTOR and ERK1/2 were distributed in the CSF-CN, and their expression levels were increased in chronic constriction injury (CCI)-induced neuropathic pain. Furthermore, the injection of both the mTOR antagonist rapamycin and the ERK1/2 antagonist U0126 into the lateral ventricle of the brain attenuated CCI-induced neuropathic pain. Inhibition of the ERK1/2 pathway had little impact on mTOR signaling, but inhibition of the mTOR pathway significantly increased ERK/2 signaling. The coadministration of rapamycin and U0126 inhibited the rapamycin-induced upregulation of ERK, and had a greater effect on pain behaviors than did the single-drug administrations. These data extend our understanding of the relationship between mTOR and ERK in the supraspinal site and demonstrate that the CSF-CN participates in neuropathic pain via the regulation of mTOR and ERK1/2.
脑脊液接触核（CSF-CN）已被证明与神经性疼痛有关，但其潜在的分子机制仍不清楚。先前的研究表明，mTOR和ERK1/2是调节神经性疼痛的重要信号通路。然而，关于这些主要通路在神经性疼痛中相互作用的研究非常罕见。因此，本研究的目的是确定CSF-CN中是否存在mTOR和ERK1/2，并阐明它们在神经性疼痛中的变化，特别是它们之间的相互作用。我们的结果表明，mTOR和ERK1/2分布在CSF-CN中，并且在慢性缩窄损伤（CCI）诱导的神经性疼痛中它们的表达水平升高。此外，将mTOR拮抗剂雷帕霉素和ERK1/2拮抗剂U0126注射到脑侧脑室可减轻CCI诱导的神经性疼痛。抑制ERK1/2通路对mTOR信号影响不大，但抑制mTOR通路显著增加ERK/2信号。雷帕霉素和U0126联合给药抑制了雷帕霉素诱导的ERK上调，并且对疼痛行为的影响比单药给药更大。这些数据扩展了我们对脊髓上水平mTOR和ERK之间关系的理解，并表明CSF-CN通过调节mTOR和ERK1/2参与神经性疼痛。
