Open AccessGeneral anesthetics activate a potent central pain-suppression circuit in the amygdala
Author(s) -
Thuy Hua,
Bin Chen,
Dongye Lu,
Kasumi Sakurai,
Shengli Zhao,
Bao-Xia Han,
Jiwoo Kim,
Luping Yin,
Yong Chen,
Jinghao Lu,
Fan Wang
Publication year - 2020
Publication title -
nature neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 13.403
H-Index - 422
eISSN - 1546-1726
pISSN - 1097-6256
DOI - 10.1038/s41593-020-0632-8
Subject(s) - neuroscience , optogenetics , population , inhibitory postsynaptic potential , amygdala , neuropathic pain , analgesic , gabaergic , medicine , premovement neuronal activity , calcium imaging , psychology , anesthesia , environmental health , calcium
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 GA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeA GA neurons. CeA GA neurons also possess basal activity that mostly reflects animals' internal state rather than external stimuli. Optogenetic activation of CeA GA 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 GA activity exacerbated pain, produced strong aversion and canceled the analgesic effect of low-dose ketamine. CeA GA neurons have widespread inhibitory projections to many affective pain-processing centers. Our study points to CeA GA as a potential powerful therapeutic target for alleviating chronic pain.