Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury.
Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling in the Insular Cortex Alleviates Neuropathic Pain after Peripheral Nerve Injury.
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DOI：
10.3389/fnmol.2017.00079
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发表时间：
2017
影响因子：
4.8
通讯作者：
Lee BH
中科院分区：
文献类型：
--
作者：
Kwon M;Han J;Kim UJ;Cha M;Um SW;Bai SJ;Hong SK;Lee BH
外周神经损伤可通过外周和中枢敏化引发神经病理性疼痛，产生异常性疼痛和痛觉过敏。最近的研究集中在岛叶皮层（IC）在神经病理性疼痛中的作用。由于IC被认为存储疼痛相关的记忆，这种结构中的翻译调节可能揭示控制慢性疼痛的新靶点。已知哺乳动物雷帕霉素靶蛋白（mTOR）可以控制mRNA翻译并影响突触可塑性，已在神经性疼痛的脊髓水平进行了研究，但在这些条件下，它在IC中的作用仍然难以捉摸。因此，本研究旨在确定mTOR信号在神经性疼痛中的作用，并评估雷帕霉素（mTORC 1抑制剂）在神经性疼痛大鼠IC中的潜在治疗作用。在神经病手术后和术后第3天和第7天将雷帕霉素微量注射到IC中后，在成年雄性Sprague-Dawley大鼠中评估机械性异常性疼痛。采用光学记录技术观察IC对周围刺激的神经反应。雷帕霉素降低机械性异常性疼痛，下调突触后密度蛋白95（PSD 95）的表达，降低IC的神经兴奋性，从而抑制神经病理性疼痛诱导的突触可塑性。这些发现表明，IC中的mTOR信号传导可能是调节神经病理性疼痛的关键分子机制。
Injury of peripheral nerves can trigger neuropathic pain, producing allodynia and hyperalgesia via peripheral and central sensitization. Recent studies have focused on the role of the insular cortex (IC) in neuropathic pain. Because the IC is thought to store pain-related memories, translational regulation in this structure may reveal novel targets for controlling chronic pain. Signaling via mammalian target of rapamycin (mTOR), which is known to control mRNA translation and influence synaptic plasticity, has been studied at the spinal level in neuropathic pain, but its role in the IC under these conditions remains elusive. Therefore, this study was conducted to determine the role of mTOR signaling in neuropathic pain and to assess the potential therapeutic effects of rapamycin, an inhibitor of mTORC1, in the IC of rats with neuropathic pain. Mechanical allodynia was assessed in adult male Sprague-Dawley rats after neuropathic surgery and following microinjections of rapamycin into the IC on postoperative days (PODs) 3 and 7. Optical recording was conducted to observe the neural responses of the IC to peripheral stimulation. Rapamycin reduced mechanical allodynia and downregulated the expression of postsynaptic density protein 95 (PSD95), decreased neural excitability in the IC, thereby inhibiting neuropathic pain-induced synaptic plasticity. These findings suggest that mTOR signaling in the IC may be a critical molecular mechanism modulating neuropathic pain.