PMID- 38530642
OWN - NLM
STAT- Publisher
LR  - 20240326
IS  - 2042-7158 (Electronic)
IS  - 0022-3573 (Linking)
DP  - 2024 Mar 26
TI  - Ciprofol alleviates remifentanil-induced hyperalgesia by regulating alpha2GABAARs, 
      NR2B, and P-CaMKIIalpha levels in the spinal cord and hippocampus.
LID - rgae027 [pii]
LID - 10.1093/jpp/rgae027 [doi]
AB  - OBJECTIVES: Several studies have shown that propofol administration during 
      surgery effectively attenuates remifentanil-induced hyperalgesia (RIH). Ciprofol, 
      a novel intravenous sedative agent analogous to propofol, has not yet been proven 
      efficacious in alleviating RIH. The present study aimed to investigate the effect 
      of ciprofol on RIH and the possible mechanisms involved. METHODS: The RIH model 
      was established by an infusion of remifentanil (1 mug.kg-1.min-1) 60 min in rats 
      with incisional pain. Ciprofol (0.1, 0.25, and 0.4 mg.kg-1.min-1) was 
      simultaneously infused to evaluate its effect on RIH. The antinociception of 
      ciprofol was verified by measured paw withdrawal mechanical threshold (PWMT) and 
      paw withdrawal thermal latency (PWTL). gamma-aminobutyric acid type A receptor alpha2 
      subunit (alpha2GABAAR), N-methyl-d-aspartate receptor NR2B subunit (NR2B), 
      calcium/calmodulin-dependent protein kinase II alpha (CaMKIIalpha), and phosphorylated 
      CaMKIIalpha (P-CaMKIIalpha) in the spinal cord and hippocampus of rats were assessed by 
      western blotting and immunohistochemistry. KEY FINDINGS: The results showed that 
      ciprofol dose-dependently increased PWMT and PWTL values in RIH rats. Moreover, 
      ciprofol upregulated alpha2GABAAR and downregulated NR2B and P-CaMKIIalpha in the rat 
      spinal cord and hippocampus. CONCLUSIONS: Ciprofol alleviates RIH effectively, 
      and the anti-hyperalgesic mechanisms may involve increasing alpha2GABAAR levels and 
      decreasing NR2B and P-CaMKIIalpha levels in the spinal cord and hippocampus.
CI  - (c) The Author(s) 2024. Published by Oxford University Press on behalf of the Royal 
      Pharmaceutical Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Yang, Yang
AU  - Yang Y
AUID- ORCID: 0009-0003-2493-7551
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
FAU - Yang, Chao
AU  - Yang C
AUID- ORCID: 0009-0007-0064-0461
AD  - Bengbu Medical University, Bengbu 233030, Anhui, China.
FAU - Shi, Yujie
AU  - Shi Y
AUID- ORCID: 0009-0000-6345-282X
AD  - Bengbu Medical University, Bengbu 233030, Anhui, China.
FAU - Tang, Chengyuan
AU  - Tang C
AUID- ORCID: 0009-0000-1489-1965
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
FAU - Wang, Hanyu
AU  - Wang H
AUID- ORCID: 0000-0002-9036-4996
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
FAU - Tan, Mengyuan
AU  - Tan M
AUID- ORCID: 0009-0009-8453-8871
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
FAU - Xing, Ruyi
AU  - Xing R
AUID- ORCID: 0000-0001-7342-3379
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
FAU - Gao, Chen
AU  - Gao C
AUID- ORCID: 0000-0002-2860-4784
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
FAU - Zhang, Min
AU  - Zhang M
AUID- ORCID: 0000-0001-5915-8214
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
FAU - Xie, Yanhu
AU  - Xie Y
AUID- ORCID: 0000-0003-1704-8249
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China, Hefei 
      230001, Anhui, China.
LA  - eng
GR  - Xiaoping Chen Foundation/
GR  - CXPJJH121003-2216/Development of Science and Technology of Hubei Province/
PT  - Journal Article
DEP - 20240326
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
SB  - IM
OTO - NOTNLM
OT  - N-methyl-d-aspartate receptors NR2B subunits
OT  - calcium/calmodulin-dependent protein kinase II alpha
OT  - ciprofol
OT  - remifentanil-induced hyperalgesia
OT  - gamma-aminobutyric acid type A receptors alpha2 subunits
EDAT- 2024/03/26 18:43
MHDA- 2024/03/26 18:43
CRDT- 2024/03/26 12:26
PHST- 2023/11/26 00:00 [received]
PHST- 2024/02/29 00:00 [accepted]
PHST- 2024/03/26 18:43 [medline]
PHST- 2024/03/26 18:43 [pubmed]
PHST- 2024/03/26 12:26 [entrez]
AID - 7635098 [pii]
AID - 10.1093/jpp/rgae027 [doi]
PST - aheadofprint
SO  - J Pharm Pharmacol. 2024 Mar 26:rgae027. doi: 10.1093/jpp/rgae027.