PMID- 25354791 OWN - NLM STAT- MEDLINE DCOM- 20160112 LR - 20181113 IS - 2041-1723 (Electronic) IS - 2041-1723 (Linking) VI - 5 DP - 2014 Oct 30 TI - Presynaptic GABAergic inhibition regulated by BDNF contributes to neuropathic pain induction. PG - 5331 LID - 10.1038/ncomms6331 [doi] LID - 5331 AB - 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. FAU - Chen, Jeremy Tsung-chieh AU - Chen JT AD - Centre for Integrative Neuroscience, Otfried-Mueller-Strasse 25, 72076 Tubingen, Germany. FAU - Guo, Da AU - Guo D AD - Centre for Integrative Neuroscience, Otfried-Mueller-Strasse 25, 72076 Tubingen, Germany. FAU - Campanelli, Dario AU - Campanelli D AD - 1] Centre for Integrative Neuroscience, Otfried-Mueller-Strasse 25, 72076 Tubingen, Germany [2] Hearing Research Centre, Elfriede Aulhornstrasse 5, 72076 Tubingen, Germany. FAU - Frattini, Flavia AU - Frattini F AD - Centre for Integrative Neuroscience, Otfried-Mueller-Strasse 25, 72076 Tubingen, Germany. FAU - Mayer, Florian AU - Mayer F AD - Centre for Integrative Neuroscience, Otfried-Mueller-Strasse 25, 72076 Tubingen, Germany. FAU - Zhou, Luming AU - Zhou L AD - Laboratory for NeuroRegeneration and Repair, Center for Neurology, Hertie Institute for Clinical Brain Research, 72076 Tubingen, Germany. FAU - Kuner, Rohini AU - Kuner R AD - Pharmacology Institute, University of Heidelberg, Im Neuenheimer Feld 584, 69120 Heidelberg, Germany. FAU - Heppenstall, Paul A AU - Heppenstall PA AD - Mouse Biology Unit, European Molecular Biology Laboratory (EMBL), Via Ramarini 32, 00016 Monterotondo, Italy. FAU - Knipper, Marlies AU - Knipper M AD - Hearing Research Centre, Elfriede Aulhornstrasse 5, 72076 Tubingen, Germany. FAU - Hu, Jing AU - Hu J AD - Centre for Integrative Neuroscience, Otfried-Mueller-Strasse 25, 72076 Tubingen, Germany. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141030 PL - England TA - Nat Commun JT - Nature communications JID - 101528555 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Receptors, GABA-A) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Ganglia, Spinal/*metabolism MH - Male MH - Mice MH - Mice, Knockout MH - Neuralgia/*etiology MH - Nociception MH - Nociceptors/*metabolism MH - Presynaptic Terminals/*metabolism MH - Receptors, GABA-A/*metabolism PMC - PMC4220496 EDAT- 2014/10/31 06:00 MHDA- 2016/01/13 06:00 PMCR- 2014/11/05 CRDT- 2014/10/31 06:00 PHST- 2014/04/29 00:00 [received] PHST- 2014/09/22 00:00 [accepted] PHST- 2014/10/31 06:00 [entrez] PHST- 2014/10/31 06:00 [pubmed] PHST- 2016/01/13 06:00 [medline] PHST- 2014/11/05 00:00 [pmc-release] AID - ncomms6331 [pii] AID - 10.1038/ncomms6331 [doi] PST - epublish SO - Nat Commun. 2014 Oct 30;5:5331. doi: 10.1038/ncomms6331.