PMID- 24792496
OWN - NLM
STAT- MEDLINE
DCOM- 20150821
LR  - 20220317
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1568
DP  - 2014 Jun 3
TI  - Effects of dexmedetomidine on P2X4Rs, p38-MAPK and BDNF in spinal microglia in 
      rats with spared nerve injury.
PG  - 21-30
LID - S0006-8993(14)00542-3 [pii]
LID - 10.1016/j.brainres.2014.04.025 [doi]
AB  - Microglia in the spinal cord is evidenced to play a crucial role in neuropathic 
      pain. Spinal P2X4 receptors (P2X4Rs), which are mainly expressed in microglia, 
      have been investigated for their roles in neuropathic pain. Dexmedetomidine 
      (DEX), a highly selective agonist of alpha2-adrenergic receptors, is clinically 
      applied to sedation and analgesia. Despite the proposed mechanisms underlying 
      DEX-induced analgesia, the possible interactions between DEX and P2X4Rs at a 
      molecular level have not been elucidated. We designated the spared nerve injury 
      (SNI) to establish the neuropathic pain model. Mechanical paw withdrawal 
      threshold (MWT) was measured to evaluate the sensitivity of neuropathic pain in 
      rats. MWT was significantly decreased in SNI rats versus control rats. 
      Expressions of spinal P2X4Rs, phosphorylated p38-mitogen-activated protein kinase 
      (p-p38-MAPK) and brain-derived neurotrophic factor (BDNF) were upregulated in SNI 
      rats. Immunofluorescence assay indicated higher densities of microglia and 
      P2X4Rs, which appeared yellow in colour, suggesting they were co-labelled. 
      Intraperitoneal injections of DEX 40mug/kg for 14 consecutive days markedly 
      reversed the SNI-induced decline of MWT; the activation of microglia was markedly 
      inhibited; in addition, the protein expressions of P2X4Rs, p-p38-MAPK and BDNF 
      were significantly downregulated. Thus, DEX could attenuate the neuropathic pain 
      in SNI rats, of which the mechanism might be related to the down-expressed 
      P2X4Rs, p-p38 and BDNF in microglia of spinal dorsal horn.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Zhou, Tian-tian
AU  - Zhou TT
AD  - Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, 
      Xuzhou, Jiangsu 221004, China. Electronic address: zhoutt0326@163.com.
FAU - Wu, Jing-ru
AU  - Wu JR
AD  - Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, 
      Xuzhou, Jiangsu 221004, China. Electronic address: wujingr5810@sina.com.
FAU - Chen, Zi-yang
AU  - Chen ZY
AD  - Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, 
      Xuzhou, Jiangsu 221004, China. Electronic address: chenzy0627@126.com.
FAU - Liu, Zhen-xiu
AU  - Liu ZX
AD  - Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, 
      Xuzhou, Jiangsu 221004, China. Electronic address: shu.19890621@163.com.
FAU - Miao, Bei
AU  - Miao B
AD  - Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, 
      Xuzhou, Jiangsu 221004, China. Electronic address: kevinpsd@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140430
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Adrenergic alpha-2 Receptor Agonists)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Receptors, Purinergic P2X4)
RN  - 67VB76HONO (Dexmedetomidine)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Adrenergic alpha-2 Receptor Agonists/pharmacology
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dexmedetomidine/*pharmacology
MH  - Disease Models, Animal
MH  - Fluorescent Antibody Technique
MH  - Hypnotics and Sedatives/*pharmacology
MH  - Injections, Intraperitoneal
MH  - Male
MH  - Microglia/*drug effects/physiology
MH  - Neuralgia/*drug therapy/physiopathology
MH  - Pain Threshold/drug effects/physiology
MH  - Rats, Sprague-Dawley
MH  - Receptors, Purinergic P2X4/metabolism
MH  - Sciatic Nerve/*injuries
MH  - Spinal Cord/*drug effects/physiopathology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - BDNF
OT  - Dexmedetomidine
OT  - Microglia
OT  - Neuropathic pain
OT  - P2X4Rs
OT  - Spinal cord
OT  - p-p38-MAPK
EDAT- 2014/05/06 06:00
MHDA- 2015/08/22 06:00
CRDT- 2014/05/06 06:00
PHST- 2014/01/17 00:00 [received]
PHST- 2014/03/29 00:00 [revised]
PHST- 2014/04/15 00:00 [accepted]
PHST- 2014/05/06 06:00 [entrez]
PHST- 2014/05/06 06:00 [pubmed]
PHST- 2015/08/22 06:00 [medline]
AID - S0006-8993(14)00542-3 [pii]
AID - 10.1016/j.brainres.2014.04.025 [doi]
PST - ppublish
SO  - Brain Res. 2014 Jun 3;1568:21-30. doi: 10.1016/j.brainres.2014.04.025. Epub 2014 
      Apr 30.