PMID- 19376198 OWN - NLM STAT- MEDLINE DCOM- 20090825 LR - 20141120 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 161 IP - 4 DP - 2009 Jul 21 TI - Long-term effects of brain-derived neurotrophic factor on the frequency of inhibitory synaptic events in the rat superficial dorsal horn. PG - 1135-43 LID - 10.1016/j.neuroscience.2009.04.030 [doi] AB - Chronic constriction injury (CCI) of rat sciatic nerve produces a specific pattern of electrophysiological changes in the superficial dorsal horn that lead to central sensitization that is associated with neuropathic pain. These changes can be recapitulated in spinal cord organotypic cultures by long term (5-6 days) exposure to brain-derived neurotrophic factor (BDNF) (200 ng/ml). Certain lines of evidence suggest that both CCI and BDNF increase excitatory synaptic drive to putative excitatory neurons while reducing that to putative inhibitory interneurons. Because BDNF slows the rate of discharge of synaptically-driven action potentials in inhibitory neurons, it should also decrease the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) throughout the superficial dorsal horn. To test this possibility, we characterized superficial dorsal horn neurons in organotypic cultures according to five electrophysiological phenotypes that included tonic, delay and irregular firing neurons. Five to 6 days of treatment with 200 ng/ml BDNF decreased sIPSC frequency in tonic and irregular neurons as might be expected if BDNF selectively decreases excitatory synaptic drive to inhibitory interneurons. The frequency of sIPSCs in delay neurons was however increased. Further analysis of the action of BDNF on tetrodotoxin-resistant miniature inhibitory postsynaptic currents (mIPSC) showed that the frequency was increased in delay neurons, unchanged in tonic neurons and decreased in irregular neurons. BDNF may thus reduce action potential frequency in those inhibitory interneurons that project to tonic and irregular neurons but not in those that project to delay neurons. FAU - Lu, V B AU - Lu VB AD - Department of Pharmacology and Centre for Neuroscience, 9.75 Medical Sciences Building, University of Alberta, Edmonton, AB T6G3E7, Canada. FAU - Colmers, W F AU - Colmers WF FAU - Smith, P A AU - Smith PA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090417 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Sodium Channel Blockers) RN - 4368-28-9 (Tetrodotoxin) SB - IM MH - Action Potentials/drug effects/physiology MH - Analysis of Variance MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology MH - In Vitro Techniques MH - Inhibitory Postsynaptic Potentials/drug effects/*physiology MH - Interneurons/physiology MH - Neurons/cytology/drug effects/physiology MH - Patch-Clamp Techniques MH - Posterior Horn Cells/drug effects/*physiology MH - Rats MH - Sciatic Neuropathy/physiopathology MH - Sodium Channel Blockers/administration & dosage MH - Synapses/drug effects/physiology MH - Tetrodotoxin/administration & dosage MH - Time Factors EDAT- 2009/04/21 09:00 MHDA- 2009/08/26 09:00 CRDT- 2009/04/21 09:00 PHST- 2009/02/27 00:00 [received] PHST- 2009/04/10 00:00 [revised] PHST- 2009/04/10 00:00 [accepted] PHST- 2009/04/21 09:00 [entrez] PHST- 2009/04/21 09:00 [pubmed] PHST- 2009/08/26 09:00 [medline] AID - S0306-4522(09)00635-6 [pii] AID - 10.1016/j.neuroscience.2009.04.030 [doi] PST - ppublish SO - Neuroscience. 2009 Jul 21;161(4):1135-43. doi: 10.1016/j.neuroscience.2009.04.030. Epub 2009 Apr 17.