KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice  

作　　者：Hao-Ran Wang Su-Wan Hu Song Zhang Yu Song Xiao-Yi Wang Lei Wang Yang-Yang Li Yu-Mei Yu He Liu Di Liu Hai-Lei Ding Jun-Li Cao 

机构地区：[1]Jiangsu Province Key Laboratory of Anesthesiology,Xuzhou Medical University,Xuzhou 221004,China [2]Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology,Xuzhou Medical University,Xuzhou 221004,China [3]Department of Anesthesiology,The First Affiliated Hospital of Nanjing Medical University(Jiangsu Province Hospital),Nanjing 210029,China [4]Department of Anesthesiology,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200000,China [5]Department of Anesthesiology,The Affiliated Hospital of Xuzhou Medical University,Xuzhou 221002,China

出　　处：《Neuroscience Bulletin》2021年第5期597-610,共14页神经科学通报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China (31771161, 81720108013, 81230025, 81200859 and 81801096);Key Project of Nature Science Foundation of Jiangsu Education Department (17KJA320005);Natural Science Foundation of Jiangsu Province (BK20171159);the Qing-Lan Project of Jiangsu, the Six Talent Summit Project of Jiangsu;the 333 High-level Personnel Training Project of Jiangsu;the Priority Academic Program Development of Jiangsu Higher Education Institutions, the Jiangsu Provincial Special Program of Medical Science (BL2014029);the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX19–2241 and KYCX20_2449), China。

摘　　要：Mesocorticolimbic dopaminergic(DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury(CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area(VTA) DA neurons projecting to the nucleus accumbens(NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception.Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex(mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc.Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.

关 键 词：NOCICEPTION Mesocorticolimbic system Ventral tegmental area Brain-derived neurotrophic factor KCNQ RETIGABINE Chronic neuropathic pain 

分 类 号：R338.3[医药卫生—人体生理学]