Department of Physiology, Yonsei University College of Medicine, 50-1, Yonsei-ro, Seodaemun-gu, 03722, Seoul, Republic of Korea.
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, 03722, Seoul, Republic of Korea.
Mol Brain. 2020 Nov 23;13(1):158. doi: 10.1186/s13041-020-00687-1.
Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic resonance imaging (MEMRI) could facilitate the visualization of the activation of pain-specific neural responses in the cerebral cortex. In order to investigate the alleviation of pain nociception by mammalian target of rapamycin (mTOR) modulation, we observed cerebrocortical excitability changes and compared regional Mn enhancement after mTOR inhibition. At day 7 after nerve injury, drugs were applied into the intracortical area, and drug (Vehicle, Torin1, and XL388) effects were compared within groups using MEMRI. Therein, signal intensities of the insular cortex (IC), primary somatosensory cortex of the hind limb region, motor cortex 1/2, and anterior cingulate cortex regions were significantly reduced after application of mTOR inhibitors (Torin1 and XL388). Furthermore, rostral-caudal analysis of the IC indicated that the rostral region of the IC was more strongly associated with pain perception than the caudal region. Our data suggest that MEMRI can depict pain-related signal changes in the brain and that mTOR inhibition is closely correlated with pain modulation in chronic pain rats.
神经损伤引起的神经性疼痛可导致慢性疼痛。最近的研究报告称，慢性疼痛会导致与疼痛相关的大脑区域的神经活动过度活跃。尽管慢性疼痛模型中与痛觉过敏和感觉异常相关的大脑活动很难用功能成像技术来表示，但锰（Mn）增强磁共振成像（MEMRI）的进步可以促进大脑皮层中疼痛特异性神经反应激活的可视化。为了研究哺乳动物雷帕霉素靶蛋白（mTOR）调节对疼痛伤害感受的缓解作用，我们观察了大脑皮质兴奋性的变化，并比较了 mTOR 抑制后的区域 Mn 增强。在神经损伤后第 7 天，将药物应用于皮质内区域，并使用 MEMRI 在组内比较药物（载体、Torin1 和 XL388）的作用。其中，应用 mTOR 抑制剂（Torin1 和 XL388）后，岛叶皮层（IC）、后肢区域初级体感皮层、运动皮层 1/2 和前扣带皮层区域的信号强度显著降低。此外，IC 的头尾部分析表明，IC 的头部区域与疼痛感知的相关性强于尾部区域。我们的数据表明，MEMRI 可以描绘大脑中与疼痛相关的信号变化，并且 mTOR 抑制与慢性疼痛大鼠的疼痛调节密切相关。
