Identification of spinal circuits involved in touch-evoked dynamic mechanical pain.
Identification of spinal circuits involved in touch-evoked dynamic mechanical pain.
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识别传输触摸引起的动态机械疼痛所需的脊髓回路
DOI：
10.1038/nn.4549
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发表时间：
2017-06
影响因子：
25
通讯作者：
Ma Q
中科院分区：
文献类型：
--
作者：
Cheng L;Duan B;Huang T;Zhang Y;Chen Y;Britz O;Garcia-Campmany L;Ren X;Vong L;Lowell BB;Goulding M;Wang Y;Ma Q
机械性超敏反应是与数百万慢性疼痛患者相关的一种衰弱症状。它以不同的形式存在，包括刷诱发的动态和丝诱发的点状。在这里，我们报道了由VGLUT3Cre和Lbx1Flpo共同表达的脊髓VT3Lbx1神经元消融后，由神经损伤或炎症引起的动态机械超敏反应在小鼠中被削弱，这表明刷诱发的有害反应和条件性地方厌恶的丧失。电生理记录显示，VT3Lbx1神经元形成吗啡抗性多突触通路，将低阈值Aβ机械感受器的输入传递到I层输出神经元。同时，在VT3Lbx1神经元消融小鼠中保存的生长抑素（SOM）谱系神经元亚群在很大程度上足以介导von Frey丝诱发的点状机械超敏反应，包括吗啡敏感型和吗啡耐药型。此外，VT3Lbx1神经元的急性沉默可以减轻由神经损伤引起的预先建立的动态机械超敏反应，这表明这些神经元是治疗这种神经性疼痛的潜在细胞靶点。
Mechanical hypersensitivity is a debilitating symptom associated with millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate. Here we report that dynamic mechanical hypersensitivity induced by nerve injury or inflammation was compromised in mice with ablation of spinal VT3Lbx1 neurons defined by coexpression of VGLUT3Cre and Lbx1Flpo, as indicated by the loss of brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3Lbx1 neurons form morphine-resistant polysynaptic pathways relaying inputs from low-threshold Aβ mechanoreceptors to lamina I output neurons. Meanwhile, the subset of somatostatin (SOM) lineage neurons preserved in VT3Lbx1 neuron-ablated mice is largely sufficient to mediate von Frey filament-evoked punctate mechanical hypersensitivity, including both morphine-sensitive and morphine-resistant forms. Furthermore, acute silencing of VT3Lbx1 neurons attenuated pre-established dynamic mechanical hypersensitivity induced by nerve injury, suggesting these neurons as a potential cellular target for treating this form of neuropathic pain.