PMID- 29867362
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 12
DP  - 2018
TI  - Inhibition of Connexin 43 and Phosphorylated NR2B in Spinal Astrocytes Attenuates 
      Bone Cancer Pain in Mice.
PG  - 129
LID - 10.3389/fncel.2018.00129 [doi]
LID - 129
AB  - Bone cancer pain (BCP) is common in patients with advanced cancers when the 
      tumors are metastasized to bone. The limited understanding of the complex 
      pathogenesis of BCP leads to the poor effectiveness of clinical treatment. 
      Previous studies have shown that astrocyte-specific connexin (Cx) 43, a forming 
      protein of gap junction (GJ) and hemichannel, and N-methyl-D-aspartate receptors 
      (NMDARs), especially the phosphorylated NMDAR 2B subunit (NR2B) phosphorylated 
      NR2B (p-NR2B) subunit are involved in BCP. However, the relationship between Cx43 
      and p-NR2B in BCP remains unclear. In the present study, we investigated the 
      expressions of Cx43, glial fibrillary acidic protein (GFAP, a marker of 
      astrocytes), and p-NR2B in the spinal dorsal horn (SDH) in a mouse model of BCP 
      established by intra-femural inoculation of Lewis lung carcinoma (LLC) cells via 
      intrathecal (ith) injection of the GJ/hemichannel blocker carbenoxolone (CARB) 
      and the NMDAR antagonist MK801, respectively. We found that the characters of BCP 
      were mimicked by intra-femural inoculation of LLC cells in mice, and the 
      expressions of Cx43, GFAP and p-NR2B in BCP mice were remarkably increased in a 
      time-dependent manner from day 7 to day 21 after cell inoculation with a gradual 
      aggravate in spontaneous pain and mechanical allodynia. Furthermore, Cx43 was 
      predominantly expressed in the spinal astrocytes. Both CARB and MK801 inhibited 
      the expressions of Cx43, GFAP and p-NR2B with attenuated pain hypersensitivity in 
      BCP mice. In addition, Cx43 was co-localized with p-NR2B in the SDH, which 
      further evidenced the presence of functional NR2B in the spinal astrocytes in BCP 
      mice. Our findings demonstrate that inhibition of Cx43 and p-NR2B in spinal 
      astrocytes could attenuate BCP in mice and Cx43 and p-NR2B in the astrocytes of 
      the SDH may play an important role via their combination action in the 
      development and maintenance of BCP in mice. These results may provide a potential 
      therapeutic target in the prevention and/or treatment of BCP.
FAU - Yang, Hui
AU  - Yang H
AD  - Department of Anesthesiology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
AD  - Department of Physiology, School of Basic Medical Science, Central South 
      University, Changsha, China.
AD  - Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, 
      Central South University, Changsha, China.
FAU - Yan, Hui
AU  - Yan H
AD  - Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 
      Changsha, China.
FAU - Li, Xin
AU  - Li X
AD  - Department of Anesthesiology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
AD  - Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, 
      Central South University, Changsha, China.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Anesthesiology, The Third Xiangya Hospital, Central South 
      University, Changsha, China.
AD  - Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, 
      Central South University, Changsha, China.
FAU - Cao, Shousong
AU  - Cao S
AD  - Department of Pharmacology, School of Pharmacy, Southwest Medical University, 
      Luzhou, China.
FAU - Huang, Baisheng
AU  - Huang B
AD  - Department of Physiology, School of Basic Medical Science, Central South 
      University, Changsha, China.
FAU - Huang, Dong
AU  - Huang D
AD  - Department of Pain, The Third Xiangya Hospital and Institute of Pain Medicine, 
      Central South University, Changsha, China.
FAU - Wu, Lixiang
AU  - Wu L
AD  - Department of Physiology, School of Basic Medical Science, Central South 
      University, Changsha, China.
LA  - eng
PT  - Journal Article
DEP - 20180508
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC5951934
OTO - NOTNLM
OT  - NMDA receptors
OT  - NR2B
OT  - astrocyte
OT  - bone cancer pain
OT  - connexin 43
OT  - mice
OT  - phosphorylation
OT  - spinal dorsal horn
EDAT- 2018/06/06 06:00
MHDA- 2018/06/06 06:01
PMCR- 2018/01/01
CRDT- 2018/06/06 06:00
PHST- 2018/01/28 00:00 [received]
PHST- 2018/04/23 00:00 [accepted]
PHST- 2018/06/06 06:00 [entrez]
PHST- 2018/06/06 06:00 [pubmed]
PHST- 2018/06/06 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2018.00129 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2018 May 8;12:129. doi: 10.3389/fncel.2018.00129. 
      eCollection 2018.