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

作者全名："Liu, Baowen; Wu, Wenyao; Cui, LingLing; Zheng, Xuemei; Li, Ningbo; Zhang, Xianwei; Duan, Guangyou"

作者地址："[Liu, Baowen; Wu, Wenyao; Zheng, Xuemei; Duan, Guangyou] Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing, Peoples R China; [Liu, Baowen; Cui, LingLing; Li, Ningbo; Zhang, Xianwei] Huazhong Univ Sci & Technol, Hubei Key LabGeriatr Anesthesia & Perioperat Brain, Wuhan, Peoples R China; [Liu, Baowen; Cui, LingLing; Li, Ningbo; Zhang, Xianwei] Huazhong Univ Sci & Technol, Tongji Hosp, Wuhan Clin Res Ctr Geriatr Anesthesia, Tongji MedicalCollege, Wuhan, Peoples R China; [Wu, Wenyao] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Anesthesiol, Wuhan, Peoples R China; [Cui, LingLing] Tongren Hosp Wuhan Univ, Wuhan Hosp 3, Dept Anesthesiol, Wuhan, Hubei, Peoples R China"

通信作者："Duan, GY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing, Peoples R China."

来源：ISCIENCE

ESI学科分类：　

WOS号：WOS:001018838000001

JCR分区：Q1

影响因子：4.6

年份：2023

卷号：26

期号：6

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结束页：　

文献类型：Article

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摘要："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."

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