PMID- 22553040
OWN - NLM
STAT- MEDLINE
DCOM- 20120625
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 32
IP  - 18
DP  - 2012 May 2
TI  - PI3-kinase/Akt pathway-regulated membrane insertion of acid-sensing ion channel 
      1a underlies BDNF-induced pain hypersensitivity.
PG  - 6351-63
LID - 10.1523/JNEUROSCI.4479-11.2012 [doi]
AB  - Central neural plasticity plays a key role in pain hypersensitivity. This process 
      is modulated by brain-derived neurotrophic factor (BDNF) and also involves the 
      type 1a acid-sensing ion channel (ASIC1a). However, the interactions between the 
      BDNF receptor, tropomyosin-related kinase B (TrkB), and ASIC1a are unclear. Here, 
      we show that deletion of ASIC1 gene suppressed the sustained mechanical 
      hyperalgesia induced by intrathecal BDNF application in mice. In both rat spinal 
      dorsal horn neurons and heterologous cell cultures, the BDNF/TrkB pathway 
      enhanced ASIC1a currents via phosphoinositide 3-kinase (PI3K)-protein kinase B 
      (PKB/Akt) cascade and phosphorylation of cytoplasmic residue Ser-25 of ASIC1a, 
      resulting in enhanced forward trafficking and increased surface expression. 
      Moreover, in both rats and mice, this enhanced ASIC1a activity was required for 
      BDNF-mediated hypersensitivity of spinal dorsal horn nociceptive neurons and 
      central mechanical hyperalgesia, a process that was abolished by intrathecal 
      application of a peptide representing the N-terminal region of ASIC1a 
      encompassing Ser-25. Thus, our results reveal a novel mechanism underlying 
      central sensitization and pain hypersensitivity, and reinforce the critical role 
      of ASIC1a channels in these processes.
FAU - Duan, Bo
AU  - Duan B
AD  - Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese 
      Academy of Sciences, Shanghai 200031, China.
FAU - Liu, Di-Shi
AU  - Liu DS
FAU - Huang, Yu
AU  - Huang Y
FAU - Zeng, Wei-Zheng
AU  - Zeng WZ
FAU - Wang, Xiang
AU  - Wang X
FAU - Yu, Hui
AU  - Yu H
FAU - Zhu, Michael X
AU  - Zhu MX
FAU - Chen, Zhe-Yu
AU  - Chen ZY
FAU - Xu, Tian-Le
AU  - Xu TL
LA  - eng
PT  - Journal Article
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 (ASIC1 protein, mouse)
RN  - 0 (Acid Sensing Ion Channels)
RN  - 0 (Asic1 protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Sodium Channels)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Acid Sensing Ion Channels
MH  - Animals
MH  - *Brain-Derived Neurotrophic Factor
MH  - Cell Membrane/*metabolism
MH  - Hyperalgesia/*chemically induced/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - Sodium Channels/*metabolism
PMC - PMC6622133
EDAT- 2012/05/04 06:00
MHDA- 2012/06/26 06:00
PMCR- 2012/11/02
CRDT- 2012/05/04 06:00
PHST- 2012/05/04 06:00 [entrez]
PHST- 2012/05/04 06:00 [pubmed]
PHST- 2012/06/26 06:00 [medline]
PHST- 2012/11/02 00:00 [pmc-release]
AID - 32/18/6351 [pii]
AID - 3765486 [pii]
AID - 10.1523/JNEUROSCI.4479-11.2012 [doi]
PST - ppublish
SO  - J Neurosci. 2012 May 2;32(18):6351-63. doi: 10.1523/JNEUROSCI.4479-11.2012.