Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction.
Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction.
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DOI：
10.1038/ncomms6331
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发表时间：
2014-10-30
影响因子：
16.6
通讯作者：
Hu, Jing
中科院分区：
文献类型：
--
作者：
Chen, Jeremy Tsung-chieh;Guo, Da;Campanelli, Dario;Frattini, Flavia;Mayer, Florian;Zhou, Luming;Kuner, Rohini;Heppenstall, Paul A.;Knipper, Marlies;Hu, Jing
门控制理论提出突触前和突触后抑制在脊髓疼痛信号处理中的重要性。然而，尽管脑源性神经营养因子（BDNF）引起的突触后解除抑制已被证明是神经性疼痛的重要机制，但突触前抑制在急性和神经性疼痛中的作用尚不清楚。本研究表明，神经损伤后，逆转电位（EGABA）的短暂转移与突触前GABAA受体电导的下降导致突触前抑制的减少。BDNF模拟，而BDNF信号阻断逆转，GABAA受体功能的改变和神经性疼痛综合征。最后，突触前抑制的遗传破坏导致行为超敏反应的自发发展，神经病变或BDNF不能进一步致敏。我们的研究结果揭示了BDNF对神经损伤后突触前gaba能抑制的新作用，可能为神经性疼痛的治疗提供了新的策略。脊髓神经活动的解除抑制与神经性疼痛有关。Chen等人的研究表明，神经活动的解除抑制是由GABA逆转电位的改变和突触前GABA电导的减少引起的，这两者都受脑源性神经营养因子的调节。
The gate control theory proposes the importance of both pre- and post-synaptic inhibition in processing pain signal in the spinal cord. However, although postsynaptic disinhibition caused by brain-derived neurotrophic factor (BDNF) has been proved as a crucial mechanism underlying neuropathic pain, the function of presynaptic inhibition in acute and neuropathic pain remains elusive. Here we show that a transient shift in the reversal potential (EGABA) together with a decline in the conductance of presynaptic GABAA receptor result in a reduction of presynaptic inhibition after nerve injury. BDNF mimics, whereas blockade of BDNF signalling reverses, the alteration in GABAA receptor function and the neuropathic pain syndrome. Finally, genetic disruption of presynaptic inhibition leads to spontaneous development of behavioural hypersensitivity, which cannot be further sensitized by nerve lesions or BDNF. Our results reveal a novel effect of BDNF on presynaptic GABAergic inhibition after nerve injury and may represent new strategy for treating neuropathic pain. Disinhibition of neural activity in the spinal cord is implicated in neuropathic pain. Chen et al. show that disinhibition of neural activity arises from a shift in reversal potential of GABA and a decrease in the conductance of presynaptic GABA, which are both regulated by brain-derived neurotrophic factor.
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影响因子：
5.3
作者：
Jovanovic, JN;Thomas, P;Moss, SJ
通讯作者：
Moss, SJ
参与体触感的蛋白质系的证据。
影响因子：
11.4
作者：
Hu, Jing;Chiang, Li-Yang;Koch, Manuel;Lewin, Gary R.
通讯作者：
Lewin, Gary R.
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：
56.9
作者：
MELZACK, R;WALL, PD
通讯作者：
WALL, PD
影响因子：
4.7
作者：
Cao XH;Chen SR;Li L;Pan HL
通讯作者：
Pan HL