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Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction

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,...

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Main Authors: Chen, Jeremy Tsung-Chieh (Author) , Guo, Da (Author) , Campanelli, Dario (Author) , Frattini, Flavia (Author) , Mayer, Florian (Author) , Zhou, Luming (Author) , Kuner, Rohini (Author) , Heppenstall, Paul A. (Author) , Knipper, Marlies (Author) , Hu, Jing (Author)
Format: Article (Journal)
Language:English
Published: 30 October 2014
In: Nature Communications
Year: 2014, Volume: 5
ISSN:2041-1723
DOI:10.1038/ncomms6331
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncomms6331
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncomms6331
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Author Notes:Jeremy Tsung-chieh Chen, Da Guo, Dario Campanelli, Flavia Frattini, Florian Mayer, Luming Zhou, Rohini Kuner, Paul A. Heppenstall, Marlies Knipper & Jing Hu
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Summary: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.
Item Description:Gesehen am 16.07.2020
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/ncomms6331

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