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General anesthetics activate a potent central pain-suppression circuit in the amygdala.
Nature Neuroscience ( IF 21.2 ) Pub Date : 2020-05-18 , DOI: 10.1038/s41593-020-0632-8
Thuy Hua 1 , Bin Chen 1 , Dongye Lu 1 , Katsuyasu Sakurai 1 , Shengli Zhao 1 , Bao-Xia Han 1 , Jiwoo Kim 1 , Luping Yin 1 , Yong Chen 2 , Jinghao Lu 1 , Fan Wang 1
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General anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeAGA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeAGA neurons. CeAGA neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeAGA potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeAGA activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeAGA neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeAGA as a potential powerful therapeutic target for alleviating chronic pain.

中文翻译:

全身麻醉药可激活杏仁核中有效的中央止痛回路。

全身麻醉(GA)可以独立于引起意识丧失而产生镇痛作用(疼痛减轻),但其潜在机制尚不清楚。我们假设GA可通过激活脊髓上镇痛回路来部分抑制疼痛。我们在小鼠中央杏仁核(CeAGA神经元)中发现了由GA激活的GABA能神经元的独特群体。体内钙成像显示不同的GA药物激活CeAGA神经元的共享集合。CeAGA神经元还具有基本活动,主要反映动物的内部状态,而不是外部刺激。CeAGA的光遗传学激活有效地抑制了由疼痛引起的自觉和跨自我感觉的行为,并消除了神经性疼痛引起的机械(超)敏感性。相反,抑制CeAGA活性会加剧疼痛,产生强烈的反感并取消了小剂量氯胺酮的镇痛作用。CeAGA神经元对许多情感性疼痛加工中心具有广泛的抑制作用。我们的研究指出CeAGA是缓解慢性疼痛的潜在强大治疗靶标。
更新日期:2020-05-18
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