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Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction.


ABSTRACT: 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.

SUBMITTER: Chen JT 

PROVIDER: S-EPMC4220496 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction.

Chen Jeremy Tsung-chieh JT   Guo Da D   Campanelli Dario D   Frattini Flavia F   Mayer Florian F   Zhou Luming L   Kuner Rohini R   Heppenstall Paul A PA   Knipper Marlies M   Hu Jing J  

Nature communications 20141030


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 o  ...[more]

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