PMID- 23884949
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20220409
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 30
DP  - 2013 Jul 24
TI  - TrkB.T1 contributes to neuropathic pain after spinal cord injury through 
      regulation of cell cycle pathways.
PG  - 12447-63
LID - 10.1523/JNEUROSCI.0846-13.2013 [doi]
AB  - Spinal cord injury (SCI) frequently causes severe, persistent central neuropathic 
      pain that responds poorly to conventional pain treatments. Brain-derived 
      neurotrophic factor (BDNF) signaling appears to contribute to central 
      sensitization and nocifensive behaviors in certain animal models of chronic pain 
      through effects mediated in part by the alternatively spliced truncated isoform 
      of the BDNF receptor tropomyosin-related kinase B.T1 (trkB.T1). Mechanisms 
      linking trkB.T1 to SCI-induced chronic central pain are unknown. Here, we 
      examined the role of trkB.T1 in central neuropathic pain after spinal cord 
      contusion. Genetic deletion of trkB.T1 in mice significantly reduced post-SCI 
      mechanical hyperesthesia, locomotor dysfunction, lesion volumes, and white matter 
      loss. Whole genome analysis, confirmed at the protein level, revealed that cell 
      cycle genes were upregulated in trkB.T1(+/+) but not trkB.T1(-/-) spinal cord 
      after SCI. TGFbeta-induced reactive astrocytes from WT mice showed increased cell 
      cycle protein expression that was significantly reduced in astrocytes from 
      trkB.T1(-/-) mice that express neither full-length trkB nor trkB.T1. 
      Administration of CR8, which selectively inhibits cyclin-dependent kinases, 
      reduced hyperesthesia, locomotor deficits, and dorsal horn (SDH) glial changes 
      after SCI, similar to trkB.T1 deletion, without altering trkB.T1 protein 
      expression. In trkB.T1(-/-) mice, CR8 had no effect. These data indicate that 
      trkB.T1 contributes to the pathobiology of SCI and SCI pain through modulation of 
      cell cycle pathways and suggest new therapeutic targets.
FAU - Wu, Junfang
AU  - Wu J
AD  - Department of Anesthesiology, School of Medicine, University of Maryland, 
      Baltimore, Maryland 21201-1579, USA.
FAU - Renn, Cynthia L
AU  - Renn CL
FAU - Faden, Alan I
AU  - Faden AI
FAU - Dorsey, Susan G
AU  - Dorsey SG
LA  - eng
GR  - R01 NR010207/NR/NINR NIH HHS/United States
GR  - R01 NR013601/NR/NINR NIH HHS/United States
GR  - R01 NS054221/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Astrocytes/cytology/physiology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Cycle/physiology
MH  - Hyperesthesia/genetics/pathology/physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuralgia/genetics/pathology/*physiopathology
MH  - Posterior Horn Cells/physiology
MH  - Primary Cell Culture
MH  - Receptor, trkB/*genetics/*metabolism
MH  - Recovery of Function/physiology
MH  - Signal Transduction/*physiology
MH  - Spinal Cord Injuries/genetics/pathology/*physiopathology
MH  - Up-Regulation/physiology
PMC - PMC3721848
EDAT- 2013/07/26 06:00
MHDA- 2013/10/18 06:00
PMCR- 2014/01/24
CRDT- 2013/07/26 06:00
PHST- 2013/07/26 06:00 [entrez]
PHST- 2013/07/26 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2014/01/24 00:00 [pmc-release]
AID - 33/30/12447 [pii]
AID - 0846-13 [pii]
AID - 10.1523/JNEUROSCI.0846-13.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Jul 24;33(30):12447-63. doi: 10.1523/JNEUROSCI.0846-13.2013.