PMID- 38390390
OWN - NLM
STAT- MEDLINE
DCOM- 20240226
LR  - 20240226
IS  - 2167-8359 (Electronic)
IS  - 2167-8359 (Linking)
VI  - 12
DP  - 2024
TI  - Xenon ameliorates chronic post-surgical pain by regulating mitophagy in microglia 
      and rats mediated by PINK1/Parkin pathway.
PG  - e16855
LID - 10.7717/peerj.16855 [doi]
LID - e16855
AB  - BACKGROUND: Chronic post-surgical pain (CPSP) is one of the important causes of 
      poor postoperative outcomes, the activation of microglia in the spinal cord is 
      closely related to the generation, transmission and maintenance of CPSP. Xenon 
      (Xe), an anesthetic gas, has been reported to be able to significantly reduce 
      intraoperative analgesia and postoperative pain sensation at low doses. However, 
      the mechanism of the regulatory effect of xenon on activated microglia after CPSP 
      remains unclear. METHODS: In this study, CPSP model rats were treated with 50% Xe 
      inhalation for 1 h following skin/muscle incision and retraction (SMIR), once a 
      day for 5 consecutive days, and then the painbehavioraltests (pain behavior 
      indexes paw withdrawal mechanical threshold, PWMT and thermal withdrawal latency, 
      TWL), microglial activation, oxidative stress-related indexes (malondialdehyde, 
      MDA; superoxide dismutase, SOD; hydrogen peroxide, H(2)O(2); and catalase, CAT), 
      mitophagy and PINK1/Parkin pathway were examined. RESULTS: The present results 
      showed that a single dose of Xe treatment in SMIR rat model could significantly 
      improve PWMT and TWL in the short-term at a single treatment and long-term at 
      multiple treatments. Xe treatment inhibited microglia activation and oxidative 
      stress in the spinal dorsal horn of SMIR rats, as indicated by the decrease of 
      Iba1 and MDA/H(2)O(2) levels and the increase of SOD/CAT levels. Compared with 
      the control group, Xe further increased the CPSP promoted Mito-Tracker (a 
      mitochondrial marker) and LC3 (an autophagy marker) co-localization positive 
      spots and PINK1/Parkin/ATG5/BECN1 (autophagy-related proteins) protein expression 
      levels, and inhibited the Mito-SOX (a mitochondrial reactive oxygen species 
      marker) positive signal, indicating that Xe promoted microglia mitophagy and 
      inhibited oxidative stress in CPSP. Mechanistically, we verified that Xe promoted 
      PINK1/Parkin signaling pathway activation. CONCLUSION: Xe plays a role in 
      ameliorating chronic post-surgical pain by regulating the PINK1/Parkin pathway 
      mediated microglial mitophagy and provide new ideas and targets for the 
      prevention and treatment of CPSP.
CI  - (c)2024 Lv et al.
FAU - Lv, Hu
AU  - Lv H
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Huang, Jiaojiao
AU  - Huang J
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Zhang, Xin
AU  - Zhang X
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - He, Zhiyong
AU  - He Z
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20240219
PL  - United States
TA  - PeerJ
JT  - PeerJ
JID - 101603425
RN  - 3H3U766W84 (Xenon)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.- (Protein Kinases)
SB  - IM
MH  - Rats
MH  - Animals
MH  - *Mitophagy
MH  - *Microglia/metabolism
MH  - Xenon/pharmacology
MH  - Hydrogen Peroxide/metabolism
MH  - Superoxide Dismutase/metabolism
MH  - Pain, Postoperative/drug therapy
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - Protein Kinases/metabolism
PMC - PMC10883148
OTO - NOTNLM
OT  - Chronic post-surgical pain
OT  - Mitophagy
OT  - PINK1/Parkin pathway
OT  - Xenon
COIS- The authors declare there are no competing interests.
EDAT- 2024/02/23 06:44
MHDA- 2024/02/26 06:43
PMCR- 2024/02/19
CRDT- 2024/02/23 03:57
PHST- 2023/06/07 00:00 [received]
PHST- 2024/01/08 00:00 [accepted]
PHST- 2024/02/26 06:43 [medline]
PHST- 2024/02/23 06:44 [pubmed]
PHST- 2024/02/23 03:57 [entrez]
PHST- 2024/02/19 00:00 [pmc-release]
AID - 16855 [pii]
AID - 10.7717/peerj.16855 [doi]
PST - epublish
SO  - PeerJ. 2024 Feb 19;12:e16855. doi: 10.7717/peerj.16855. eCollection 2024.