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 Mn2+ 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.

中文翻译：

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锰增强 MRI 显示慢性疼痛大鼠 mTOR 抑制后大脑对伤害感受的反应减少

由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，由于慢性疼痛，大脑中与伤害相关的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异常性疼痛相关的大脑活动难以用功能成像技术表示，但锰 (Mn) 增强磁共振成像 (MEMRI) 的进步可以促进疼痛特异性神经反应激活的可视化。大脑皮层。为了研究哺乳动物雷帕霉素靶标 (mTOR) 调节对疼痛伤害感受的缓解，我们观察了脑皮质兴奋性变化并比较了 mTOR 抑制后局部 Mn2+ 增强。在神经损伤后第 7 天，将药物应用于皮质内区域，药物（Vehicle，使用 MEMRI 在组内比较 Torin1 和 XL388) 的影响。其中，在应用 mTOR 抑制剂（Torin1 和 XL388）后，岛叶皮层 (IC)、后肢区域初级躯体感觉皮层、运动皮层 1/2 和前扣带回皮层区域的信号强度显着降低。此外，IC 的头端-尾端分析表明，与尾端区域相比，IC 的头端区域与疼痛感知的相关性更强。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。应用 mTOR 抑制剂（Torin1 和 XL388）后，前扣带回皮层区域显着减少。此外，IC 的头端-尾端分析表明 IC 的头端区域比尾端区域与疼痛感知的相关性更强。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。应用 mTOR 抑制剂（Torin1 和 XL388）后，前扣带回皮层区域显着减少。此外，IC 的头端-尾端分析表明，与尾端区域相比，IC 的头端区域与疼痛感知的相关性更强。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。