PMID- 34988165
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220429
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 9
IP  - 22
DP  - 2021 Nov
TI  - Exchange proteins directly activated by cyclic adenosine monophosphate inhibitor 
      reverses mechanical allodynia via the modification of astrocytes activity in the 
      spinal cord.
PG  - 1656
LID - 10.21037/atm-21-5384 [doi]
LID - 1656
AB  - BACKGROUND: Gliosis and inflammation are pivotal in the development of acute and 
      chronic pain. Here, we demonstrated a previously unidentified molecular mechanism 
      in which the activation of exchange proteins directly activated by cyclic 
      adenosine monophosphate (Epac)1 accelerated the activation of astrocytes in the 
      spinal cord, thereby promoting chronic postsurgical pain (CPSP). METHODS: We 
      established a rat model of CPSP induced by skin/muscle incision and retraction 
      (SMIR). Pain behaviors were assessed using mechanical withdrawal threshold (MWT) 
      at different times. The lumbosacral enlargement of the spinal cord was isolated 
      to detect the expression of Epac1 and the activity of astrocytes. They were 
      assessed using western blot and immunofluorescence staining. RESULTS: SMIR 
      induced persistent mechanical hyperalgesia after surgery. This hyperalgesia 
      response was prolonged to more than 21 d after surgery. The time course of spinal 
      Epac1 upregulation was correlated with SMIR-induced pain behaviors. Meanwhile, 
      Epac1 immunoreactivity was colocalized primarily with astrocytes but not with 
      microglial cells or neurons on 7 d after surgery. Intrathecal injection of Epac1 
      inhibitor CE3F4 significantly suppressed SMIR-induced mechanical allodynia and 
      activation of astrocytes in the spinal cord. This analgesic effect of single-dose 
      administration of CE3F4 lasted up to 6 h and wore off at 12 h after injection. 
      CONCLUSIONS: Spinal Epac1-mediated activation of astrocytes may facilitate CPSP. 
      Inhibition of Epac1 may effectively prevent CPSP.
CI  - 2021 Annals of Translational Medicine. All rights reserved.
FAU - She, Qing
AU  - She Q
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Chen, Junjie
AU  - Chen J
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Zhong, Chaochao
AU  - Zhong C
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Huang, Saisai
AU  - Huang S
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Lu, Cui'e
AU  - Lu C
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      China.
FAU - Qin, Yibin
AU  - Qin Y
AD  - Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, 
      China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC8667141
OTO - NOTNLM
OT  - Epac1
OT  - astrocytes
OT  - chronic postsurgical pain (CPSP)
OT  - skin/muscle incision and retraction (SMIR)
OT  - spinal cord
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at https://dx.doi.org/10.21037/atm-21-5384). All authors report 
      that this research was supported by the National Natural Science Foundation of 
      China (81701106) and the Subsidized Projects of Nantong Science and Technology 
      Bureau (JC2018055). The authors have no other conflicts of interest to declare.
EDAT- 2022/01/07 06:00
MHDA- 2022/01/07 06:01
PMCR- 2021/11/01
CRDT- 2022/01/06 06:00
PHST- 2021/08/22 00:00 [received]
PHST- 2021/11/09 00:00 [accepted]
PHST- 2022/01/06 06:00 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/01/07 06:01 [medline]
PHST- 2021/11/01 00:00 [pmc-release]
AID - atm-09-22-1656 [pii]
AID - 10.21037/atm-21-5384 [doi]
PST - ppublish
SO  - Ann Transl Med. 2021 Nov;9(22):1656. doi: 10.21037/atm-21-5384.