PMID- 28668500
OWN - NLM
STAT- MEDLINE
DCOM- 20180803
LR  - 20180803
IS  - 1872-8111 (Electronic)
IS  - 0168-0102 (Linking)
VI  - 125
DP  - 2017 Dec
TI  - Toll-like receptor-4/p38 MAPK signaling in the dorsal horn contributes to P2X4 
      receptor activation and BDNF over-secretion in cancer induced bone pain.
PG  - 37-45
LID - S0168-0102(16)30336-4 [pii]
LID - 10.1016/j.neures.2017.06.006 [doi]
AB  - Our previous research suggested that the P2X4 receptor (P2X4R) expression in 
      microglia was involved in the activation of toll-like receptor-4 (TLR4) in the 
      dorsal horn in the rat model of cancer induced bone pain (CIBP). In this study, 
      we focused on whether TLR4- mitogen-activated protein kinases, p38 (p38 MAPK) 
      contributes to P2X4R activation and brain-derived neurotrophic factor (BDNF) 
      over-secretion in CIBP. In in vitro experiment, the results showed that BDNF 
      expression evoked by ATP stimulation was dependent on TLR4-p38. In in vivo 
      experiment, the results demonstrated that an intrathecal injection of TLR4 siRNA 
      alleviated nociception induced by lipopolysaccharide (LPS) plus ATP or CIBP with 
      decreased expression of P2X4R, TLR4, BDNF, interleukin-6 (IL-6) and 
      phosphorylated-p38 MAPK (p-p38 MAPK). Moreover, injection with p38MAPK inhibitor 
      SB203580 resulted in an identical pattern compared with treatment with TLR4 
      siRNA. Our results demonstrate that the activation of TLR4-p38MAPK-P2X4R 
      signaling in microglial possibility plays an important role in the process of 
      nociceptive transmission in CIBP, suggesting new mechanism and potential 
      therapeutic targets for CIBP.
CI  - Copyright (c) 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights 
      reserved.
FAU - Meng, Xiao-Wen
AU  - Meng XW
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou City, Jiangsu Province, China. Electronic address: 
      lingximxw@163.com.
FAU - Gao, Jian-Ling
AU  - Gao JL
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou City, Jiangsu Province, China. Electronic address: 
      gjlsz7883@163.com.
FAU - Zuo, Jian-Ling
AU  - Zuo JL
AD  - Brain Research Laboratory, The First Affiliated Hospital of Soochow University, 
      Suzhou City, Jiangsu Province, China. Electronic address: jzuo919@126.com.
FAU - Wang, Li-Na
AU  - Wang LN
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou City, Jiangsu Province, China. Electronic address: 
      wangln@suda.edu.cn.
FAU - Liu, Si-Lan
AU  - Liu SL
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou City, Jiangsu Province, China. Electronic address: 
      szliusl@126.com.
FAU - Jin, Xiao-Hong
AU  - Jin XH
AD  - Department of Anesthesiology, The First Affiliated Hospital of Soochow 
      University, Suzhou City, Jiangsu Province, China. Electronic address: 
      kxhwsy@163.com.
FAU - Yao, Ming
AU  - Yao M
AD  - Department of Anesthesiology, The First Affiliated Hospital of Jiaxing 
      University, Jiaxing, Zhejiang, China. Electronic address: jxyaoming@163.com.
FAU - Namaka, Michael
AU  - Namaka M
AD  - College of Pharmacy, University of Manitoba, Apotex Centre, 319- 750 McDermot 
      Avenue, Winnipeg, Manitoba, Canada. Electronic address: namakamp@ms.umanitoba.ca.
LA  - eng
PT  - Journal Article
DEP - 20170628
PL  - Ireland
TA  - Neurosci Res
JT  - Neuroscience research
JID - 8500749
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Purinergic P2X4)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/drug therapy/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Female
MH  - Humans
MH  - Lipopolysaccharides/pharmacology
MH  - Microglia/drug effects/*metabolism
MH  - Pain/metabolism
MH  - Rats, Sprague-Dawley
MH  - Receptors, Purinergic P2X4/drug effects/*metabolism
MH  - Spinal Cord Dorsal Horn/drug effects/metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/drug effects/*metabolism
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Cancer induced bone pain
OT  - Microglia
OT  - P2X4 receptors
OT  - Phosphorylated-p38 MAPK
OT  - Toll-like receptor-4
EDAT- 2017/07/03 06:00
MHDA- 2018/08/04 06:00
CRDT- 2017/07/03 06:00
PHST- 2016/12/26 00:00 [received]
PHST- 2017/06/19 00:00 [revised]
PHST- 2017/06/22 00:00 [accepted]
PHST- 2017/07/03 06:00 [pubmed]
PHST- 2018/08/04 06:00 [medline]
PHST- 2017/07/03 06:00 [entrez]
AID - S0168-0102(16)30336-4 [pii]
AID - 10.1016/j.neures.2017.06.006 [doi]
PST - ppublish
SO  - Neurosci Res. 2017 Dec;125:37-45. doi: 10.1016/j.neures.2017.06.006. Epub 2017 
      Jun 28.