Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Brain Res. 2020 Apr 15;1733:146720. doi: 10.1016/j.brainres.2020.146720. Epub 2020 Feb 14.
In the pain matrix, the insular cortex (IC) is mainly involved in discriminative sensory and motivative emotion. Abnormal signal transmission from injury site causes neuropathic pain, which generates enhanced synaptic plasticity. The mammalian target of rapamycin (mTOR) complex is the key regulator of protein synthesis; it is involved in the modulation of synaptic plasticity. To date, there has been no report on the changes in optical signals in the IC under neuropathic condition after treatment with mTOR inhibitors, such as Torin1 and XL388. Therefore, we aimed to determine the pain-relieving effect of mTOR inhibitors (Torin1 and XL388) and observe the changes in optical signals in the IC after treatment. Mechanical threshold was measured in adult male Sprague-Dawley rats after neuropathic surgery, and therapeutic effect of inhibitors was assessed on post-operative day 7 following the microinjection of Torin1 or XL388 into the IC. Optical signals were acquired to observe the neuronal activity of the IC in response to peripheral stimulation before and after treatment with mTOR inhibitors. Consequently, the inhibitors showed the most effective alleviation 4 h after microinjection into the IC. In optical imaging, peak amplitudes of optical signals and areas of activated regions were reduced after treatment with Torin1 and XL388. However, there were no significant optical signal changes in the IC before and after vehicle application. These findings suggested that Torin1 and XL388 are associated with the alleviation of neuronal activity that is excessively manifested in the IC, and is assumed to diminish synaptic plasticity.
在疼痛矩阵中，脑岛皮层（IC）主要参与辨别感觉和动机情绪。损伤部位的异常信号传递导致神经性疼痛，从而产生增强的突触可塑性。哺乳动物雷帕霉素靶蛋白（mTOR）复合物是蛋白质合成的关键调节剂；它参与调节突触可塑性。迄今为止，还没有关于 mTOR 抑制剂（如 Torin1 和 XL388）治疗后神经性疼痛条件下 IC 光信号变化的报道。因此，我们旨在确定 mTOR 抑制剂（Torin1 和 XL388）的镇痛效果，并观察治疗后 IC 中光信号的变化。在神经病理性手术后，成年雄性 Sprague-Dawley 大鼠测量机械阈值，并在微注射 Torin1 或 XL388 到 IC 后第 7 天评估抑制剂的治疗效果。获取光信号以观察 mTOR 抑制剂治疗前后 IC 神经元活动对周围刺激的反应。结果表明，抑制剂在微注射到 IC 后 4 小时显示出最有效的缓解作用。在光学成像中，Torin1 和 XL388 处理后光信号的峰值幅度和激活区域的面积减小。然而，在载体应用前后，IC 中没有明显的光学信号变化。这些发现表明，Torin1 和 XL388 与过度表现的 IC 中神经元活动的缓解有关，并且假设其可以减少突触可塑性。
