Department of Neurobiology, Duke University Medical Center, Durham, NC, USA.
Department of Neurology, Duke University Medical Center, Durham, NC, USA.
Nat Neurosci. 2020 Jul;23(7):854-868. doi: 10.1038/s41593-020-0632-8. Epub 2020 May 18.
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 (CeA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeA neurons. CeA neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeA potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeA activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeA neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeA as a potential powerful therapeutic target for alleviating chronic pain.
全身麻醉（GA）可以产生镇痛（疼痛丧失），而不诱导意识丧失，但潜在的机制仍不清楚。我们假设 GA 通过激活脊髓上的镇痛回路来部分抑制疼痛。我们发现，在小鼠的中央杏仁核（CeA 神经元）中，存在一种由 GA 激活的独特的 GABA 能神经元群体。体内钙成像显示，不同的 GA 药物激活了 CeA 中的共享神经元集合。CeA 神经元也具有基础活动，主要反映动物的内部状态，而不是外部刺激。光遗传学激活 CeA 有力地抑制了感觉模态中的疼痛诱发的反射性和自我恢复行为，并消除了神经病理性疼痛引起的机械（超敏）敏感性。相反，抑制 CeA 活动会加剧疼痛，产生强烈的厌恶感，并取消小剂量氯胺酮的镇痛效果。CeA 神经元对许多情感疼痛处理中心有广泛的抑制性投射。我们的研究表明，CeA 可能是缓解慢性疼痛的一个有潜力的强大治疗靶点。
