Microglial voltage-dependent anion channel 1 signaling modulates sleep deprivation-induced transition to chronic postsurgical pain.

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY Sleep Pub Date : 2023-11-08 DOI:10.1093/sleep/zsad039

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

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引用次数: 2

Abstract

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-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: 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.

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小胶质细胞电压依赖性阴离子通道1信号调节睡眠剥夺诱导的慢性术后疼痛的转变。

研究目的:本研究证实了皮肤/肌肉切开和收缩(SMIR)手术前后的睡眠剥夺增加了慢性疼痛的风险，并研究了小胶质电压依赖性阴离子通道1 (VDAC1)信号的潜在作用。方法:从SMIR前1天到手术后第三天，成年小鼠接受6小时的完全睡眠剥夺。在手术前和术后21天内评估机械疼痛和热诱发疼痛。测量小胶质细胞的激活、VDAC1表达和寡聚化的变化。注射二甲胺四环素，观察抑制小胶质细胞活化对疼痛维持的影响。采用VDAC1抑制剂4,4'-二异硫氰酸二苯乙烯-2,2'-二磺酸(DIDS)和寡聚化抑制剂VBIT-4来测定VDAC1信号在小胶质腺苷5'三磷酸(ATP)释放、炎症(IL-1β和CCL2)和慢性疼痛中的作用。结果:睡眠剥夺显著增加SMIR手术后疼痛持续时间，激活小胶质细胞，增强脊髓VDAC1信号。二甲胺四环素抑制小胶质细胞激活，减轻睡眠剥夺引起的疼痛维持。脂多糖(LPS)诱导的小胶质细胞活化伴随着VDAC1表达和寡聚化的增加，与对照组相比，细胞膜表面的VDAC1增加。DIDS和VBIT-4可挽救lps诱导的小胶质细胞ATP释放和IL-1β和CCL2表达。在小鼠中，DIDS和VBIT-4逆转了睡眠缺失引起的小胶质细胞激活和疼痛的慢性性，类似于二甲胺四环素的作用。米诺环素联合VBIT-4或DIDS未发现协同效应。结论:围手术期睡眠剥夺激活了脊髓小胶质细胞，增加了小鼠术后慢性疼痛的风险。VDAC1信号调节小胶质细胞激活相关的ATP释放、炎症和慢性疼痛。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Sleep 医学-临床神经学

CiteScore

10.10

自引率

10.70%

发文量

1134

审稿时长

3 months

期刊介绍： SLEEP® publishes findings from studies conducted at any level of analysis, including: Genes Molecules Cells Physiology Neural systems and circuits Behavior and cognition Self-report SLEEP® publishes articles that use a wide variety of scientific approaches and address a broad range of topics. These may include, but are not limited to: Basic and neuroscience studies of sleep and circadian mechanisms In vitro and animal models of sleep, circadian rhythms, and human disorders Pre-clinical human investigations, including the measurement and manipulation of sleep and circadian rhythms Studies in clinical or population samples. These may address factors influencing sleep and circadian rhythms (e.g., development and aging, and social and environmental influences) and relationships between sleep, circadian rhythms, health, and disease Clinical trials, epidemiology studies, implementation, and dissemination research.