Chronic pain is a major health problem, affecting 10-30% of the population in developed countries. While chronic pain is defined as "a persistent complaint of pain lasting for more than the usual period for recovery," recently accumulated lines of evidence based on human brain imaging have revealed that chronic pain is not simply a sustained state of nociception, but rather an allostatic state established through gradually progressing plastic changes in the central nervous system. To visualize the brain activity associated with spontaneously occurring pain during the shift from acute to chronic pain under anesthetic-free conditions, we used manganese-enhanced magnetic resonance imaging (MEMRI) with a 9.4-T scanner to visualize neural activity-dependent accumulation of manganese in the brains of mice with hind paw inflammation. Time-differential analysis between 2- and 6-h after formalin injection to the left hind paw revealed a significantly increased MEMRI signal in various brain areas, including the right insular cortex, right nucleus accumbens, right globus pallidus, bilateral caudate putamen, right primary/secondary somatosensory cortex, bilateral thalamus, right amygdala, bilateral substantial nigra, and left ventral tegmental area. To analyze the role of the right amygdala in these post-formalin MEMRI signals, we repeatedly inhibited right amygdala neurons during this 2-6-h period using the "designer receptors exclusively activated by designer drugs" (DREADD) technique. Pharmacological activation of inhibitory DREADDs expressed in the right amygdala significantly attenuated MEMRI signals in the bilateral infralimbic cortex, bilateral nucleus accumbens, bilateral caudate putamen, right globus pallidus, bilateral ventral tegmental area, and bilateral substantia nigra, suggesting that the inflammatory pain-associated activation of these structures depends on the activity of the right amygdala and DREADD-expressing adjacent structures. In summary, the combined use of DREADD and MEMRI is a promising approach for revealing regions associated with spontaneous pain-associated brain activities and their causal relationships.

中文翻译：

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杏仁核在自发性炎性疼痛相关的疼痛网络激活中的主要作用-一种化学成因锰增强的MRI方法。

慢性疼痛是一个主要的健康问题，在发达国家影响了10％至30％的人口。虽然将慢性疼痛定义为“持续持续的疼痛持续时间超过通常的恢复期”，但最近根据人脑影像学积累的证据表明，慢性疼痛不仅仅是简单的持续伤害感受，而是一种持续的伤害感受。通过逐渐发展中枢神经系统的塑性变化来建立同种异体状态。为了可视化在无麻醉条件下从急性疼痛转变为慢性疼痛期间与自发性疼痛相关的大脑活动，我们使用了带有9.4-T扫描仪的锰增强磁共振成像（MEMRI）来可视化神经活动依赖性锰的积累在后爪发炎的老鼠的大脑中 向左后爪注射福尔马林后2小时至6小时之间的时差分析显示，在各个大脑区域，包括右岛皮层，右伏核，右苍白球，双侧尾状壳，右原发性脑，MEMRI信号均显着增加/次级体感皮层，双侧丘脑，右杏仁核，双侧实质性黑质和左腹被盖区。为了分析右杏仁核在这些福尔马林后MEMRI信号中的作用，我们在此2-6-h期间使用“仅由设计药物激活的设计受体”（DREADD）技术反复抑制了右杏仁核神经元。右侧杏仁核中表达的抑制性DREADDs的药理激活显着减弱了双侧下肢皮层，双侧伏隔核中的MEMRI信号，双侧尾状壳核，右苍白球，双侧腹侧被盖区和双侧黑质，提示这些结构的炎性疼痛相关激活取决于右杏仁核和表达DREADD的相邻结构的活性。总而言之，DREADD和MEMRI的组合使用是揭示与疼痛相关的自发性脑活动及其因果关系的区域的有前途的方法。