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Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction

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Listed:
  • Jeremy Tsung-chieh Chen

    (Centre for Integrative Neuroscience)

  • Da Guo

    (Centre for Integrative Neuroscience)

  • Dario Campanelli

    (Centre for Integrative Neuroscience
    Hearing Research Centre)

  • 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)

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.

Suggested Citation

  • Jeremy Tsung-chieh Chen & Da Guo & Dario Campanelli & Flavia Frattini & Florian Mayer & Luming Zhou & Rohini Kuner & Paul A. Heppenstall & Marlies Knipper & Jing Hu, 2014. "Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6331
    DOI: 10.1038/ncomms6331
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