Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction

被引:0
|
作者
Jeremy Tsung-chieh Chen
Da Guo
Dario Campanelli
Flavia Frattini
Florian Mayer
Luming Zhou
Rohini Kuner
Paul A. Heppenstall
Marlies Knipper
Jing Hu
机构
[1] Centre for Integrative Neuroscience,
[2] Hearing Research Centre,undefined
[3] Laboratory for NeuroRegeneration and Repair,undefined
[4] Center for Neurology,undefined
[5] Hertie Institute for Clinical Brain Research,undefined
[6] Pharmacology Institute,undefined
[7] University of Heidelberg,undefined
[8] Mouse Biology Unit,undefined
[9] European Molecular Biology Laboratory (EMBL),undefined
来源
Nature Communications | / 5卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
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.
引用
收藏
相关论文
共 50 条
  • [31] GABAergic Inhibition Regulated Pain Sensitization through STEP61 Signaling in Spinal Dorsal Horn of Mice
    Li, Lu
    Shi, Lei
    Xu, Ying-Ming
    Yang, Xian
    Suo, Zhan-Wei
    Hu, Xiao-Dong
    ANESTHESIOLOGY, 2015, 122 (03) : 686 - 697
  • [32] Presynaptic modulation of GABAergic inhibition by GABAB receptors in the rat's inferior colliculus
    Ma, CL
    Kelly, JB
    Wu, SH
    NEUROSCIENCE, 2002, 114 (01) : 207 - 215
  • [33] Loss of Striatonigral GABAergic Presynaptic Inhibition Enables Motor Sensitization in Parkinsonian Mice
    Borgkvist, Anders
    Avegno, Elizabeth M.
    Wong, Minerva Y.
    Kheirbek, Mazen A.
    Sonders, Mark S.
    Hen, Rene
    Sulzer, David
    NEURON, 2015, 87 (05) : 976 - 988
  • [34] PRESYNAPTIC INHIBITION OF GABAERGIC SYNAPTIC TRANSMISSION BY ADENOSINE IN MOUSE HYPOTHALAMIC HYPOCRETIN NEURONS
    Xia, J. X.
    Xiong, J. X.
    Wang, H. K.
    Duan, S. M.
    Ye, J. N.
    Hu, Z. A.
    NEUROSCIENCE, 2012, 201 : 46 - 56
  • [35] Presynaptic inhibition of gabaergic miniature currents by metabotropic glutamate receptor in the rat CNS
    Doi, A
    Ishibashi, H
    Jinno, S
    Kosaka, T
    Akaike, N
    NEUROSCIENCE, 2002, 109 (02) : 299 - 311
  • [36] Sortilin gates neurotensin and BDNF signaling to control peripheral neuropathic pain
    Richner, Mette
    Pallesen, Lone T.
    Ulrichsen, Maj
    Poulsen, Ebbe T.
    Holm, Thomas H.
    Login, Hande
    Castonguay, Annie
    Lorenzo, Louis-Etienne
    Goncalves, Nadia P.
    Andersen, Olav M.
    Lykke-Hartmann, Karin
    Enghild, Jan J.
    Ronn, Lars C. B.
    Malik, Ibrahim J.
    De Koninck, Yves
    Bjerrum, Ole J.
    Vaegter, Christian B.
    Nykjaer, Anders
    SCIENCE ADVANCES, 2019, 5 (06)
  • [37] Nitric Oxide Signaling Contributes to Ectopic Orofacial Neuropathic Pain
    Sugiyama, T.
    Shinoda, M.
    Watase, T.
    Honda, K.
    Ito, R.
    Kaji, K.
    Urata, K.
    Lee, J.
    Ohara, K.
    Takahashi, O.
    Echizenya, S.
    Iwata, K.
    JOURNAL OF DENTAL RESEARCH, 2013, 92 (12) : 1113 - 1117
  • [38] CROSSTALK BETWEEN SPINAL ASTROCYTES AND NEURONS CONTRIBUTES TO NEUROPATHIC PAIN
    Wang, W.
    Wu, S. X.
    Li, Y. Q.
    GLIA, 2009, 57 (13) : S28 - S28
  • [39] Maladaptive Dendritic Spine Remodeling Contributes to Diabetic Neuropathic Pain
    Tan, Andrew M.
    Samad, Omar A.
    Fischer, Tanya Z.
    Zhao, Peng
    Persson, Anna-Karin
    Waxman, Stephen G.
    JOURNAL OF NEUROSCIENCE, 2012, 32 (20): : 6795 - 6807
  • [40] The complement cascade in spinal cord microglia contributes to neuropathic pain
    Woolf, Clifford J.
    NEURON GLIA BIOLOGY, 2007, 2 : S15 - S15