Abstract | STUDY OBJECTIVES: METHODS: Adult mice received 6 hours of total sleep deprivation from 1 day prior to SMIR until the third day after surgery. Mechanical and heat-evoked pain was assessed before and within 21 days after surgery. Microglial activation and changes in VDAC1 expression and oligomerization were measured. Minocycline was injected to observe the effects of inhibiting microglial activation on pain maintenance. The VDAC1 inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid ( DIDS) and oligomerization inhibitor VBIT-4 were used to determine the roles of VDAC1 signaling on microglial adenosine 5' triphosphate ( ATP) release, inflammation (IL-1β and CCL2), and chronicity of pain. RESULTS:
Sleep deprivation significantly increased the pain duration after SMIR surgery, activated microglia, and enhanced VDAC1 signaling in the spinal cord. Minocycline inhibited microglial activation and alleviated sleep deprivation-induced pain maintenance. Lipopolysaccharide (LPS)-induced microglial activation was accompanied by increased VDAC1 expression and oligomerization, and more VDAC1 was observed on the cell membrane surface compared with control. DIDS and VBIT-4 rescued LPS-induced microglial ATP release and IL-1β and CCL2 expression. DIDS and VBIT-4 reversed sleep loss-induced microglial activation and pain chronicity in mice, similar to the effects of minocycline. No synergistic effects were found for minocycline plus VBIT-4 or DIDS. CONCLUSIONS:
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Authors | Shi-Nan Wei, Hao Zhang, Yan Lu, Hui-Jie Yu, Tao Ma, Si-Nian Wang, Kun Yang, Mou-Li Tian, Ai-Hua Huang, Wei Wang, Feng-Sheng Li, Yong-Wang Li |
Journal | Sleep
(Sleep)
Vol. 46
Issue 11
(11 08 2023)
ISSN: 1550-9109 [Electronic] United States |
PMID | 36827092
(Publication Type: Journal Article)
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Copyright | © The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: [email protected]. |
Chemical References |
- Voltage-Dependent Anion Channel 1
- Minocycline
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
- Lipopolysaccharides
- Adenosine Triphosphate
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Topics |
- Mice
- Animals
- Microglia
(metabolism)
- Sleep Deprivation
(complications, metabolism)
- Voltage-Dependent Anion Channel 1
(metabolism)
- Minocycline
(pharmacology, metabolism)
- 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
(metabolism)
- Lipopolysaccharides
(metabolism)
- Pain, Postoperative
- Inflammation
(metabolism)
- Adenosine Triphosphate
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