扣带皮层中的蛋白激酶 Cγ神经元参与神经病理性痛觉过敏和与疼痛相关的情绪的发展。

The PKCγ neurons in anterior cingulate cortex contribute to the development of neuropathic allodynia and pain-related emotion.

机构信息

Department of Pain Medicine, Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, 12644Fourth Military Medical University, Xian, China.

出版信息

Mol Pain. 2021 Jan-Dec;17:17448069211061973. doi: 10.1177/17448069211061973.

DOI:10.1177/17448069211061973

PMID:34898326

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8679404/

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

We conclude that the PKCγ neurons in ACC are closely linked with neuropathic allodynia and pain-related emotional behaviors.

摘要

背景

脊髓背角的蛋白激酶 Cγ（PKCγ）神经元在神经性痛觉过敏中起着不可或缺的作用，但大脑区域的 PKCγ神经元在神经性疼痛中的确切作用仍不清楚。越来越多的研究表明，前扣带皮层（ACC）与疼痛感知和行为密切相关，本研究旨在探讨 ACC 中的 PKCγ 神经元对新开发的 Prkcg-P2A-Tdtomato 小鼠神经性痛觉过敏和与疼痛相关的情绪的贡献。

方法

使用 c-fos 表达来监测 CCI（坐骨神经慢性缩窄性损伤）诱导的神经性疼痛状态下 PKCγ 的活性。通过化学遗传学激活或沉默 ACC PKCγ 神经元，观察疼痛行为的变化。通过膜片钳全细胞记录比较正常和 CCI 小鼠 ACC PKCγ 神经元的兴奋性。

结果

PKCγ-Tdtomato 神经元主要分布在 ACC 的 III-V 层。通过细胞内染色证实，Tdtomato 主要表达在 ACC 锥体神经元中。CCI 小鼠对无害刺激的 ACC PKCγ 神经元的 c-fos 表达明显升高。膜片钳记录显示，CCI 小鼠的 ACC PKCγ-Tdtomato 神经元被大量激活。在 Prkcg-icre 小鼠中激活 ACC PKCγ 神经元会引起机械性痛觉过敏和与疼痛相关的厌恶行为，相反，在 CCI 条件下沉默它们会显著逆转机械性痛觉过敏和与疼痛相关的厌恶行为。