A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.
A Brainstem-Spinal Cord Inhibitory Circuit for Mechanical Pain Modulation by GABA and Enkephalins.
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DOI：
10.1016/j.neuron.2017.01.008
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发表时间：
2017-02-22
期刊：
影响因子：
16.2
通讯作者：
Scherrer G
中科院分区：
文献类型：
--
作者：
François A;Low SA;Sypek EI;Christensen AJ;Sotoudeh C;Beier KT;Ramakrishnan C;Ritola KD;Sharif-Naeini R;Deisseroth K;Delp SL;Malenka RC;Luo L;Hantman AW;Scherrer G
疼痛阈值部分地被设定为情绪和内部状态的函数，其通过脊髓中伤害性传递的下行调制来实现。延髓头端腹内侧区（RVM）的神经元被认为对这一过程有重要贡献;然而，RVM神经元的不同群体促进或减少疼痛的神经回路和突触机制仍然难以捉摸。在这里，我们使用在体内的光学/化学遗传操作和跨突触跟踪的遗传识别的背角和RVM神经元，以揭示RVM脊髓初级传入电路控制疼痛阈值。出乎意料的是，我们发现RVM GABA能神经元通过抑制背角脑啡肽能/GABA能中间神经元来促进机械性疼痛。我们进一步证明，这些interneurons门的感觉输入和控制疼痛，通过时间协调脑啡肽和GABA介导的突触前抑制体感神经元。我们的研究结果揭示了一个下行的双突触抑制回路，它促进了机械性疼痛，在压力期间参与，并且可以有针对性地建立更高的疼痛阈值。François等人发现了一个控制机械疼痛阈值的神经回路。他们证明GABA能脑干神经元调节脊髓中内源性阿片样脑啡肽的释放，以调节感觉疼痛纤维的输入。
Pain thresholds are, in part, set as a function of emotional and internal states by descending modulation of nociceptive transmission in the spinal cord. Neurons of the rostral ventromedial medulla (RVM) are thought to critically contribute to this process; however, the neural circuits and synaptic mechanisms by which distinct populations of RVM neurons facilitate or diminish pain remain elusive. Here we used in vivo opto/chemogenetic manipulations and trans-synaptic tracing of genetically identified dorsal horn and RVM neurons to uncover an RVM-spinal cord-primary afferent circuit controlling pain thresholds. Unexpectedly, we found that RVM GABAergic neurons facilitate mechanical pain by inhibiting dorsal horn enkephalinergic/GABAergic interneurons. We further demonstrate that these interneurons gate sensory inputs and control pain through temporally coordinated enkephalin- and GABA-mediated presynaptic inhibition of somatosensory neurons. Our results uncover a descending disynaptic inhibitory circuit that facilitates mechanical pain, is engaged during stress, and could be targeted to establish higher pain thresholds. François et al. identified a neural circuit that controls mechanical pain thresholds. They demonstrated that GABAergic brainstem neurons regulate the release of the endogenous opioid enkephalin in the spinal cord to modulate inputs from sensory pain fibers.
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影响因子：
64.5
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
通讯作者：
Ma Q
影响因子：
5.2
作者：
Bardoni R;Takazawa T;Tong CK;Choudhury P;Scherrer G;Macdermott AB
通讯作者：
Macdermott AB
影响因子：
16.2
作者：
Foster, Edmund;Wildner, Hendrik;Tudeau, Laetitia;Haueter, Sabine;Ralvenius, William T.;Jegen, Monika;Johannssen, Helge;Hoesli, Ladina;Haenraets, Karen;Ghanem, Alexander;Conzelmann, Karl-Klaus;Boesl, Michael;Zeilhofer, Hanns Ulrich
通讯作者：
Zeilhofer, Hanns Ulrich
影响因子：
5.3
作者：
Baker, Kenneth B.;Schuster, Daniel;Cooperrider, Jessica;Machado, Andre G.
通讯作者：
Machado, Andre G.
影响因子：
3.3
作者：
Antal, M;Petko, M;StormMathisen, J
通讯作者：
StormMathisen, J