Highly synchronized cortical circuit dynamics mediate spontaneous pain in mice.
Highly synchronized cortical circuit dynamics mediate spontaneous pain in mice.
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DOI：
10.1172/jci166408
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发表时间：
2023-03-01
影响因子：
15.9
通讯作者：
Shen, Shiqian
中科院分区：
文献类型：
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作者：
Ding, Weihua;Fischer, Lukas;Chen, Qian;Li, Ziyi;Yang, Liuyue;You, Zerong;Hu, Kun;Wu, Xinbo;Zhou, Xue;Chao, Wei;Hu, Peter;Dagnew, Tewodros Mulugeta;Dubreuil, Daniel M.;Wang, Shiyu;Xia, Suyun;Bao, Caroline;Zhu, Shengmei;Chen, Lucy;Wang, Changning;Wainger, Brian;Jin, Peng;Mao, Jianren;Feng, Guoping;Harnett, Mark T.;Shen, Shiqian
皮质神经动力学介导大脑皮质的信息处理，这涉及基本的生物过程，如视觉和嗅觉，以及神经和精神疾病。自发性疼痛是人类神经病理性疼痛的关键特征。自发性疼痛是否会使皮层网络进入异常状态，如果是的话，它是否能恢复到“正常”的工作范围以改善疼痛，这是未知的。使用临床相关的神经性疼痛与自发性疼痛样行为的小鼠模型，我们报告说，orofacial自发性疼痛激活了一个特定的区域内的初级躯体感觉皮层（S1），显示同步的神经动力学活体双光子钙成像揭示。局部GABA能中间神经元活动减退是这种同步化的基础。疼痛诱导的皮层同步可以通过操纵局部S1网络或临床有效的疼痛治疗来减弱。具体而言，化学发生抑制疼痛相关的c-Fos表达神经元和选择性激活GABA能中间神经元显着衰减S1同步。临床有效的疼痛治疗，包括卡马西平和神经根减压术也可以抑制S1同步。更重要的是，通过减弱疼痛引起的S1同步来恢复神经动力学的“正常”范围，减轻了疼痛样行为。这些结果表明，自发性疼痛推动S1区域网络进入同步状态，而这种同步的逆转减轻了疼痛。
Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a “normal” operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain–like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos–expressing neurons and selective activation of GABAergic interneurons significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More important, restoring a “normal” range of neural dynamics through attenuation of pain-induced S1 synchronization alleviated pain-like behavior. These results suggest that spontaneous pain pushed the S1 regional network into a synchronized state, whereas reversal of this synchronization alleviated pain.