Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain.
Identification of Early RET+ Deep Dorsal Spinal Cord Interneurons in Gating Pain.
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DOI：
10.1016/j.neuron.2016.07.038
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发表时间：
2016-09-07
期刊：
影响因子：
16.2
通讯作者：
Luo, Wenqin
中科院分区：
文献类型：
--
作者：
Cui, Lian;Miao, Xuerong;Liang, Lingli;Abdus-Saboor, Ishmail;Olson, William;Fleming, Michael S.;Ma, Minghong;Tao, Yuan-Xiang;Luo, Wenqin
痛觉的门控制理论(GCT)认为，痛觉神经元和触觉神经元通过脊髓背角门控神经元相互拮抗。然而，GCT背后的确切神经回路在很大程度上仍然难以捉摸。在这里，我们鉴定了一组新的深层脱氢酶(DDH)抑制中间神经元，它们在新生儿中表达受体酪氨酸激酶Ret。这些早期的RET+DDH神经元从触摸和/或痛觉传入接受兴奋性和多突触抑制性输入。此外，它们还通过突触前和突触后抑制负向调节痛觉和触觉通路。最后，早期RET+DDH神经元的特异性消融增加了基础和慢性疼痛，而它们的急性激活则减少了基础痛觉，缓解了炎症性和神经病理性疼痛。综上所述，我们的发现揭示了一种新的脊髓回路，它介导了触摸和疼痛通路之间的串扰，并表明一些早期的RET+DDH神经元可能起到疼痛“门控”神经元的作用。
The gate control theory (GCT) of pain proposes that pain- and touch-sensing neurons antagonize each other through spinal cord dorsal horn (DH) gating neurons. However, the exact neural circuits underlying the GCT remain largely elusive. Here, we identified a new population of deep layer DH (dDH) inhibitory interneurons that express the receptor tyrosine kinase Ret neonatally. These early RET+ dDH neurons receive excitatory as well as polysynaptic inhibitory inputs from touch- and/or pain-sensing afferents. In addition, they negatively regulate DH pain and touch pathways through both pre- and postsynaptic inhibition. Finally, specific ablation of early RET+ dDH neurons increases basal and chronic pain, whereas their acute activation reduces basal pain perception and relieves inflammatory and neuropathic pain. Taken together, our findings uncover a novel spinal circuit that mediates crosstalk between touch and pain pathways and suggest that some early RET+ dDH neurons could function as pain “gating” neurons.
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影响因子：
64.5
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Zeilhofer, Hanns Ulrich
影响因子：
3.7
作者：
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通讯作者：
Luo, Wenqin
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作者：
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