The PKCγ neurons in anterior cingulate cortex contribute to the development of neuropathic allodynia and pain-related emotion.
The PKCγ neurons in anterior cingulate cortex contribute to the development of neuropathic allodynia and pain-related emotion.
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DOI：
10.1177/17448069211061973
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发表时间：
2021-01
期刊：
影响因子：
3.3
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Zhang X;Liu P;He X;Jiang Z;Wang Q;Gu N;Lu Y
尽管脊髓背角的PKCγ神经元在神经病理性异常性疼痛中起着不可或缺的作用，但脑区的PKCγ神经元在神经病理性疼痛中的确切作用尚不清楚。近年来，前扣带皮层（anterior cingulate cortex，ACC）与疼痛感知和疼痛行为密切相关，本研究旨在探讨前扣带皮层PKCγ神经元在Prkcg-P2 A-Tdtomato小鼠神经病理性异常性疼痛和疼痛相关情绪中的作用。采用慢性坐骨神经压迫性损伤（CCI）致神经病理性疼痛模型，以c-fos蛋白表达为指标，观察慢性坐骨神经压迫性疼痛模型中蛋白激酶C γ（PKCγ）活性的变化。采用化学遗传学方法激活或沉默ACC PKCγ神经元，观察痛行为的变化。通过膜片钳全细胞记录比较了正常和CCI小鼠ACC PKCγ神经元的兴奋性。PKCγ-Tdtomato神经元主要分布于ACC的III-V层，胞内染色显示Tdtomato主要表达于ACC锥体神经元。CCI小鼠ACC PKCγ神经元c-fos表达明显增加。膜片钳记录显示CCI小鼠ACC PKCγ-Tdtomato神经元大量激活。Prkcg-icre小鼠ACC PKCγ神经元的化学发生激活可诱导机械性异常性疼痛和疼痛相关的位置厌恶行为，而CCI条件下ACC PKC γ神经元的沉默可显著逆转机械性异常性疼痛和疼痛相关的位置厌恶行为。结论ACC中PKCγ神经元与神经病理性异常性疼痛及疼痛相关情绪行为密切相关。
While the PKCγ neurons in spinal dorsal horn play an indispensable part in neuropathic allodynia, the exact effect of PKCγ neurons of brain regions in neuropathic pain remains elusive. Mounting research studies have depicted that the anterior cingulate cortex (ACC) is closely linked with pain perception and behavior, the present study was designed to investigate the contribution of PKCγ neurons in ACC to neuropathic allodynia and pain-related emotion in newly developed Prkcg-P2A-Tdtomato mice. The c-fos expression in response to innocuous stimulation was used to monitor the activity of PKCγ in CCI (chronic constriction injury of the sciatic nerve) induced neuropathic pain condition. Activating or silencing ACC PKCγ neurons by chemogenetics was applied to observe the changes of pain behavior. The excitability of ACC PKCγ neurons in normal and CCI mice was compared by patch-clamp whole-cell recordings. The PKCγ-Tdtomato neurons were mainly distributed in layer III-Vof ACC. The Tdtomato was mainly expressed in ACC pyramidal neurons demonstrated by intracellular staining. The c-fos expression in ACC PKCγ neurons in response to innocuous stimulation was obviously elevated in CCI mice. The patch clamp recordings showed that ACC PKCγ-Tdtomato neurons were largely activated in CCI mice. Chemogenetic activation of ACC PKCγ neurons in Prkcg-icre mice induced mechanical allodynia and pain-related aversive behavior, conversely, silencing them in CCI condition significantly reversed the mechanical allodynia and pain-related place aversive behavior. We conclude that the PKCγ neurons in ACC are closely linked with neuropathic allodynia and pain-related emotional behaviors.
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影响因子：
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作者：
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影响因子：
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作者：
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