Dorsal Horn Circuits for Persistent Mechanical Pain.
Dorsal Horn Circuits for Persistent Mechanical Pain.
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持续机械疼痛的背喇叭电路。
DOI：
10.1016/j.neuron.2015.07.029
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发表时间：
2015-08-19
期刊：
影响因子：
16.2
通讯作者：
Seal RP
中科院分区：
文献类型：
--
作者：
Peirs C;Williams SP;Zhao X;Walsh CE;Gedeon JY;Cagle NE;Goldring AC;Hioki H;Liu Z;Marell PS;Seal RP
在受伤或疾病的情况下发生的持续性机械超敏反应仍然是一个主要的临床问题，很大程度上是因为潜在的神经回路仍然未知。在这里，我们报告了用于机械异常性疼痛的难以捉摸的背角电路关键组件的功能识别。我们发现，机械性疼痛需要由背角深部的离散神经元群短暂表达 VGLUT3，并且成人中细胞的激活会传达机械超敏反应。这些接收直接低阈值输入的单元指向电路启动的新位置。随后对 c-Fos 的分析表明，该回路向背侧延伸至伤害感受层 I 投射神经元，并包括层 II 钙视网膜蛋白神经元，我们发现这些神经元也能传达机械性异常性疼痛。最后，利用炎症和神经性疼痛模型，我们发现背角中的多个微电路编码这种形式的疼痛。
Persistent mechanical hypersensitivity that occurs in the setting of injury or disease remains a major clinical problem largely because the underlying neural circuitry is still not known. Here we report the functional identification of key components of the elusive dorsal horn circuit for mechanical allodynia. We show that the transient expression of VGLUT3 by a discrete population of neurons in the deep dorsal horn is required for mechanical pain and that activation of the cells in the adult conveys mechanical hypersensitivity. The cells, which receive direct low threshold input, point to a novel location for circuit initiation. Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes lamina II calretinin neurons, which we show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain.