PMID- 27287221
OWN - NLM
STAT- MEDLINE
DCOM- 20170309
LR  - 20200124
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 59
IP  - 4
DP  - 2016 Aug
TI  - Effect of Epac1 on pERK and VEGF Activation in Postoperative Persistent Pain in 
      Rats.
PG  - 554-64
LID - 10.1007/s12031-016-0776-x [doi]
AB  - The function of guanine nucleotide exchange protein conversion factor (Epac1) in 
      regenerating nerves, stimulating insulin release, controlling vascular pressure, 
      and controlling other metabolic activities has been recognized; however, few 
      studies have addressed the potential role of Epac1 in controlling chronic 
      postoperative pain. Using a rat model of skin/muscle incision and retraction 
      (SMIR), our study tested the hypothesis that increased Epac1 signaling is a 
      factor in postoperative chronic pain. Rats were randomly divided into normal, 
      sham operation, SMIR, SMIR + Epac1 siRNA (Epac1 inhibitor), and normal + 8-pCPT 
      (Epac1 agonist) groups. The mechanical withdrawal threshold (MWT) was used as an 
      index of pain sensitivity. Epac1 expression in the incision-site muscle, DRG, and 
      spinal cord was assessed using western blotting and immunofluorescence. The 
      effects of Epac1 agonists and Epac1 siRNA on MWT and phosphorylated extracellular 
      signal-regulated kinase (pERK), vascular endothelial growth factor (VEGF), 
      protein release in the spinal cord, and DRG levels were also studied. SMIR 
      increased Epac1 expression in the incision-site muscle, spinal cord, and DRG, and 
      decreased MWT. 8-pCPT induced the development of hypersensitivity and increased 
      pERK and VEGF expression in normal rats, whereas siRNA decreased the expression 
      of pERK and VEGF. This study suggests that activation of the Epac1 signal might 
      induce local postoperative recovery process, which could be an important 
      mechanism by which to control postoperative chronic pain. Our data suggest that 
      therapy targeted at decreasing Epac1 levels provides promise for the prevention 
      and treatment of chronic postoperative pain.
FAU - Cao, Su
AU  - Cao S
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, No.20 
      Xisi Road, Nantong, Jiangsu, 226001, People's Republic of China.
FAU - Bian, Zhen
AU  - Bian Z
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, No.20 
      Xisi Road, Nantong, Jiangsu, 226001, People's Republic of China.
AD  - Nantong University, No.19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic 
      of China.
FAU - Zhu, Xiang
AU  - Zhu X
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, No.20 
      Xisi Road, Nantong, Jiangsu, 226001, People's Republic of China.
FAU - Shen, Shi-Ren
AU  - Shen SR
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, No.20 
      Xisi Road, Nantong, Jiangsu, 226001, People's Republic of China. 
      823312378@qq.com.
LA  - eng
PT  - Journal Article
DEP - 20160610
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Guanine Nucleotide Exchange Factors)
RN  - 0 (Rapgef3 protein, rat)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Chronic Pain/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/*metabolism
MH  - Ganglia, Spinal/metabolism
MH  - Guanine Nucleotide Exchange Factors/agonists/genetics/*metabolism
MH  - Male
MH  - Pain, Postoperative/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord/metabolism
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
OTO - NOTNLM
OT  - Chronic postoperative pain
OT  - Epac1
OT  - VEGF
OT  - pERK
EDAT- 2016/06/12 06:00
MHDA- 2017/03/10 06:00
CRDT- 2016/06/12 06:00
PHST- 2016/02/24 00:00 [received]
PHST- 2016/06/02 00:00 [accepted]
PHST- 2016/06/12 06:00 [entrez]
PHST- 2016/06/12 06:00 [pubmed]
PHST- 2017/03/10 06:00 [medline]
AID - 10.1007/s12031-016-0776-x [pii]
AID - 10.1007/s12031-016-0776-x [doi]
PST - ppublish
SO  - J Mol Neurosci. 2016 Aug;59(4):554-64. doi: 10.1007/s12031-016-0776-x. Epub 2016 
      Jun 10.