Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction

Jeremy Tsung-chieh Chen, Da Guo, Dario Campanelli, Flavia Frattini, Florian Mayer, Luming Zhou, Rohini Kuner, Paul A. Heppenstall, Marlies Knipper and Jing Hu ()
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Jeremy Tsung-chieh Chen: Centre for Integrative Neuroscience
Da Guo: Centre for Integrative Neuroscience
Dario Campanelli: Centre for Integrative Neuroscience
Flavia Frattini: Centre for Integrative Neuroscience
Florian Mayer: Centre for Integrative Neuroscience
Luming Zhou: Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research
Rohini Kuner: Pharmacology Institute, University of Heidelberg
Paul A. Heppenstall: Mouse Biology Unit, European Molecular Biology Laboratory (EMBL)
Marlies Knipper: Hearing Research Centre
Jing Hu: Centre for Integrative Neuroscience

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6331

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