PMID- 23466809
OWN - NLM
STAT- MEDLINE
DCOM- 20131113
LR  - 20130426
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 240
DP  - 2013 Jun 14
TI  - Epigenetic regulation of BDNF expression in the primary sensory neurons after 
      peripheral nerve injury: implications in the development of neuropathic pain.
PG  - 147-54
LID - S0306-4522(13)00194-2 [pii]
LID - 10.1016/j.neuroscience.2013.02.053 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is known to be up-regulated in the 
      dorsal root ganglion (DRG) after peripheral nerve injury, and to contribute to 
      neuropathic pain. Here, we found that thermal hyperalgesia and mechanical 
      allodynia at day 7 post-injury were inhibited only when anti-BDNF antibody was 
      intrathecally administrated at day 2 post-injury. Consistent with behavioral 
      results, Western blot analysis showed that the expression levels of BDNF protein 
      in the spinal dorsal horn were markedly induced during early stage post-injury. 
      Moreover, the maximal increase in BDNF mRNA expression in the DRG was observed at 
      day 1 post-injury, and significantly elevated levels were sustained for at least 
      14 days. Four of five BDNF mRNA transcripts were up-regulated after nerve injury, 
      and the most inducible transcript was exon I. Using a chromatin 
      immunoprecipitation (ChIP) assay, we found that nerve injury promotes histone H3 
      and H4 acetylation, transcriptionally active modifications, at BDNF promoter I at 
      day 1 post-injury, and the levels of histone acetylation remain elevated for at 
      least 7 days. Taken together, our findings suggest that an initial increase in 
      BDNF exon I expression controlled by epigenetic mechanisms might have a crucial 
      role in the development of neuropathic pain.
CI  - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Uchida, H
AU  - Uchida H
AD  - Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate 
      School of Biomedical Sciences, Nagasaki, Japan.
FAU - Matsushita, Y
AU  - Matsushita Y
FAU - Ueda, H
AU  - Ueda H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130304
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antibodies)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Antibodies/administration & dosage
MH  - Brain-Derived Neurotrophic Factor/genetics/immunology/*metabolism
MH  - Chromatin Immunoprecipitation
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic/*physiology
MH  - Exons/genetics
MH  - Injections, Spinal
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuralgia/*etiology
MH  - Pain Measurement
MH  - Pain Threshold/drug effects/physiology
MH  - Peripheral Nerve Injuries/*complications/*pathology
MH  - RNA, Messenger/genetics
MH  - Sensory Receptor Cells/*metabolism
MH  - Time Factors
EDAT- 2013/03/08 06:00
MHDA- 2013/11/14 06:00
CRDT- 2013/03/08 06:00
PHST- 2012/10/05 00:00 [received]
PHST- 2013/02/19 00:00 [revised]
PHST- 2013/02/20 00:00 [accepted]
PHST- 2013/03/08 06:00 [entrez]
PHST- 2013/03/08 06:00 [pubmed]
PHST- 2013/11/14 06:00 [medline]
AID - S0306-4522(13)00194-2 [pii]
AID - 10.1016/j.neuroscience.2013.02.053 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Jun 14;240:147-54. doi: 10.1016/j.neuroscience.2013.02.053. 
      Epub 2013 Mar 4.