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
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: Original Articles
• 页码范围: 597-610
• 页数: 14页
• 语种: 英文

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.