Identification of spinal circuits transmitting and gating mechanical pain.

Identification of spinal circuits transmitting and gating mechanical pain.
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识别传输和控制机械疼痛的脊髓回路

DOI:
10.1016/j.cell.2014.11.003
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发表时间:
2014-12-04
期刊:
影响因子:
64.5
通讯作者:
Ma Q
Ma Q
中科院分区:
生物学1区
文献类型:
--
作者:
Duan B;Cheng L;Bourane S;Britz O;Padilla C;Garcia-Campmany L;Krashes M;Knowlton W;Velasquez T;Ren X;Ross S;Lowell BB;Wang Y;Goulding M;Ma Q

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脊髓中的疼痛处理被假定依赖于接受来自伤害感受器和Aβ机械感受器的输入的伤害性传递(T)神经元,其中Aβ输入通过脊髓抑制性神经元(IN)的前馈激活门控。在这里,我们使用交叉遗传操作,以确定这些疼痛转导的关键组成部分。标记和消融脊髓兴奋性和抑制性神经元的六个群体,再加上行为和电生理分析,表明表达生长抑素(SOM)的兴奋性神经元代表T型细胞,其消融导致机械性疼痛的损失。以强啡肽(Dyn)表达为标志的抑制性神经元代表IN型神经元,其是门控Aβ纤维激活SOM+神经元引起疼痛所必需的。因此,外周机械伤害感受器和Aβ机械感受器与脊髓SOM+兴奋性和Dyn+抑制性神经元一起形成传递和门控机械疼痛的微回路。
Pain processing in the spinal cord has been postulated to rely on nociceptive transmission (T) neurons receiving inputs from nociceptors and Aβ mechanoreceptors, with Aβ inputs gated through feed-forward activation of spinal inhibitory neurons (IN). Here we used intersectional genetic manipulations to identify these critical components of pain transduction. Marking and ablating six populations of spinal excitatory and inhibitory neurons, coupled with behavioral and electrophysiological analysis, showed that excitatory neurons expressing somatostatin (SOM) represent T-type cells, whose ablation causes loss of mechanical pain. Inhibitory neurons marked by the expression of dynorphin (Dyn) represent IN-type neurons, which are necessary to gate Aβ fibers from activating SOM+ neurons to evoke pain. Therefore, peripheral mechanical nociceptors and Aβ mechanoreceptors, together with spinal SOM+ excitatory and Dyn+ inhibitory neurons form a microcircuit that transmits and gates mechanical pain.
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