PMID- 24966334 OWN - NLM STAT- MEDLINE DCOM- 20150219 LR - 20211021 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 289 IP - 32 DP - 2014 Aug 8 TI - Persistent inflammation-induced up-regulation of brain-derived neurotrophic factor (BDNF) promotes synaptic delivery of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA1 subunits in descending pain modulatory circuits. PG - 22196-204 LID - 10.1074/jbc.M114.580381 [doi] AB - The enhanced AMPA receptor phosphorylation at GluA1 serine 831 sites in the central pain-modulating system plays a pivotal role in descending pain facilitation after inflammation, but the underlying mechanisms remain unclear. We show here that, in the rat brain stem, in the nucleus raphe magnus, which is a critical relay in the descending pain-modulating system of the brain, persistent inflammatory pain induced by complete Freund adjuvant (CFA) can enhance AMPA receptor-mediated excitatory postsynaptic currents and the GluA2-lacking AMPA receptor-mediated rectification index. Western blot analysis showed an increase in GluA1 phosphorylation at Ser-831 but not at Ser-845. This was accompanied by an increase in distribution of the synaptic GluA1 subunit. In parallel, the level of histone H3 acetylation at bdnf gene promoter regions was reduced significantly 3 days after CFA injection, as indicated by ChIP assays. This was correlated with an increase in BDNF mRNA levels and BDNF protein levels. Sequestering endogenous extracellular BDNF with TrkB-IgG in the nucleus raphe magnus decreased AMPA receptor-mediated synaptic transmission and GluA1 phosphorylation at Ser-831 3 days after CFA injection. Under the same conditions, blockade of TrkB receptor functions, phospholipase C, or PKC impaired GluA1 phosphorylation at Ser-831 and decreased excitatory postsynaptic currents mediated by GluA2-lacking AMPA receptors. Taken together, these results suggest that epigenetic up-regulation of BDNF by peripheral inflammation induces GluR1 phosphorylation at Ser-831 sites through activation of the phospholipase C-PKC signaling cascade, leading to the trafficking of GluA1 to pain-modulating neuronal synapses. CI - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Tao, Wenjuan AU - Tao W AD - From the Key Laboratory of Brain Functions and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China and the Department of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui 241000, China. FAU - Chen, Quan AU - Chen Q AD - From the Key Laboratory of Brain Functions and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China and. FAU - Zhou, Wenjie AU - Zhou W AD - From the Key Laboratory of Brain Functions and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China and. FAU - Wang, Yunping AU - Wang Y AD - From the Key Laboratory of Brain Functions and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China and. FAU - Wang, Lu AU - Wang L AD - From the Key Laboratory of Brain Functions and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China and. FAU - Zhang, Zhi AU - Zhang Z AD - From the Key Laboratory of Brain Functions and Diseases, School of Life Science, University of Science and Technology of China, Hefei, Anhui 230027, China and zhizhang@ustc.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140625 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - 0 (Receptors, AMPA) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.4.- (Type C Phospholipases) RN - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*physiology MH - Epigenesis, Genetic MH - Excitatory Postsynaptic Potentials MH - Inflammation/genetics/*physiopathology MH - Male MH - Nucleus Raphe Magnus/*physiopathology MH - Pain/genetics/*physiopathology MH - Promoter Regions, Genetic MH - Protein Kinase C/metabolism MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, trkB/metabolism MH - Receptors, AMPA/chemistry/*physiology MH - Signal Transduction MH - Synaptic Transmission MH - Type C Phospholipases/metabolism MH - Up-Regulation PMC - PMC4139232 OTO - NOTNLM OT - BDNF OT - Epigenetics OT - GluA1 OT - Pain EDAT- 2014/06/27 06:00 MHDA- 2015/02/20 06:00 PMCR- 2015/08/08 CRDT- 2014/06/27 06:00 PHST- 2014/06/27 06:00 [entrez] PHST- 2014/06/27 06:00 [pubmed] PHST- 2015/02/20 06:00 [medline] PHST- 2015/08/08 00:00 [pmc-release] AID - S0021-9258(20)33157-4 [pii] AID - M114.580381 [pii] AID - 10.1074/jbc.M114.580381 [doi] PST - ppublish SO - J Biol Chem. 2014 Aug 8;289(32):22196-204. doi: 10.1074/jbc.M114.580381. Epub 2014 Jun 25.