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A novel co-target of ACY1 governing plasma membrane translocation of SphK1 contributes to inflammatory and neuropathic pain

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机构： [1]Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China [2]Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [3]Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China [4]Department of Anesthesiology, Wuhan third Hospital/Tongren Hospital of Wuhan University, Wuhan, Hubei Province, China

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Previous studies validate that inhibiting sodium channel 1.8 (Nav1.8) effectively relieves inflammatory and neuropathic pain. However, Nav1.8 blockers have cardiac side effects in addition to analgesic effects. Here, we constructed a spinal differential protein expression profile using Nav1.8 knockout mice to screen common downstream proteins of Nav1.8 in inflammatory and neuropathic pain. We found that aminoacylase 1 (ACY1) expression was increased in wild-type mice compared to Nav1.8 knockout mice in both pain models. Moreover, spinal ACY1 overexpression induced mechanical allodynia in naive mice, while ACY1 suppression alleviated inflammatory and neuropathic pain. Further, ACY1 could interact with sphingosine kinase 1 and promote its membrane translocation, resulting in sphingosine-1-phosphate upregulation and the activation of glutamatergic neurons and astrocytes. In conclusion, ACY1 acts as a common downstream effector protein of Nav1.8 in inflammatory and neuropathic pain and could be a new and precise therapeutic target for chronic pain.© 2023 The Author(s).

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出版当年[2022]版：

大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

最新[2023]版：

大类 | 2 区综合性期刊

小类 | 2 区综合性期刊

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出版当年[2021]版：

Q1 MULTIDISCIPLINARY SCIENCES

最新[2023]版：

Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 4.6 最新[2023版] 5 最新五年平均 6.107 出版当年[2021版] 6.233 出版当年五年平均 5.458 出版前一年[2020版] 5.8 出版后一年[2022版]

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第一作者机构： [1]Department of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China [2]Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

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