PMID- 36827092 OWN - NLM STAT- MEDLINE DCOM- 20231113 LR - 20240112 IS - 1550-9109 (Electronic) IS - 0161-8105 (Linking) VI - 46 IP - 11 DP - 2023 Nov 8 TI - Microglial voltage-dependent anion channel 1 signaling modulates sleep deprivation-induced transition to chronic postsurgical pain. LID - zsad039 [pii] LID - 10.1093/sleep/zsad039 [doi] AB - STUDY OBJECTIVES: This study verified that sleep deprivation before and after skin/muscle incision and retraction (SMIR) surgery increased the risk of chronic pain and investigated the underlying roles of microglial voltage-dependent anion channel 1 (VDAC1) signaling. 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-1beta 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-1beta 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: Perioperative sleep deprivation activated spinal microglia and increases the risk of chronic postsurgical pain in mice. VDAC1 signaling regulates microglial activation-related ATP release, inflammation, and chronicity of pain. CI - (c) The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Wei, Shi-Nan AU - Wei SN AD - The Postgraduate Training Base of Jinzhou Medical University, Beijing, China. AD - Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Zhang, Hao AU - Zhang H AD - Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Lu, Yan AU - Lu Y AD - Department of Neurology, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Yu, Hui-Jie AU - Yu HJ AD - Department of Nuclear Radiation Injury and Monitoring, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Ma, Tao AU - Ma T AD - Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Wang, Si-Nian AU - Wang SN AD - Department of Nuclear Radiation Injury and Monitoring, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Yang, Kun AU - Yang K AD - The Postgraduate Training Base of Jinzhou Medical University, Beijing, China. FAU - Tian, Mou-Li AU - Tian ML AD - Department of Anesthesiology, Changzheng Hospital Affiliate to the Naval Medical University, Shanghai, China. FAU - Huang, Ai-Hua AU - Huang AH AD - Department of Neurology, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Wang, Wei AU - Wang W AD - Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Li, Feng-Sheng AU - Li FS AD - Department of Nuclear Radiation Injury and Monitoring, The PLA Rocket Force Characteristic Medical Center, Beijing, China. FAU - Li, Yong-Wang AU - Li YW AD - Department of Anesthesiology, The Third people's Hospital of Longgang District, Shenzhen, China. LA - eng GR - 82171203/National Natural Science Foundation of China/ GR - AEP17J001/CPLA Key Project for Medical Sciences/ GR - LGKCYLWS2021000034/Longgang District Science and Technology Development Foundation of Shenzhen/ PT - Journal Article PL - United States TA - Sleep JT - Sleep JID - 7809084 RN - EC 1.6.- (Voltage-Dependent Anion Channel 1) RN - FYY3R43WGO (Minocycline) RN - Q1O6DSW23R (4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid) RN - 0 (Lipopolysaccharides) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Mice MH - Animals MH - *Microglia/metabolism MH - *Sleep Deprivation/complications/metabolism MH - Voltage-Dependent Anion Channel 1/metabolism MH - Minocycline/pharmacology/metabolism MH - 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/metabolism MH - Lipopolysaccharides/metabolism MH - Pain, Postoperative MH - Inflammation/metabolism MH - Adenosine Triphosphate OTO - NOTNLM OT - chronic postsurgical pain OT - microglia OT - skin/muscle incision and retraction (SMIR) OT - sleep deprivation OT - voltage-dependent anion channel 1 EDAT- 2023/02/25 06:00 MHDA- 2023/11/13 06:43 CRDT- 2023/02/24 12:22 PHST- 2022/09/15 00:00 [received] PHST- 2023/01/30 00:00 [revised] PHST- 2023/11/13 06:43 [medline] PHST- 2023/02/25 06:00 [pubmed] PHST- 2023/02/24 12:22 [entrez] AID - 7056772 [pii] AID - 10.1093/sleep/zsad039 [doi] PST - ppublish SO - Sleep. 2023 Nov 8;46(11):zsad039. doi: 10.1093/sleep/zsad039.