Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula
Why depression and pain often coexist and mutually reinforce: Role of the lateral habenula
复制标题
为什么抑郁和疼痛经常共存并相互加强：外侧缰核的作用
DOI：
10.1016/j.expneurol.2016.08.010
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发表时间：
2016-10-01
影响因子：
5.3
通讯作者：
Zhao, Hua
中科院分区：
文献类型：
--
作者：
Li, Jicheng;Li, Yang;Zhao, Hua
抑郁症和疼痛之间的相互关系越来越受到人们的关注。尽管侧链（LHb）在抑郁和疼痛的发病机制中广泛涉及，但其在抑郁和疼痛相互作用中的作用尚不清楚。因此，本研究旨在探讨LHb在大鼠抑郁-疼痛共病中的作用。采用单胞外放电记录和免疫荧光法比较正常大鼠和模型大鼠LHb神经元的放电率和c-Fos表达。在后爪皮下注射福尔马林以模拟自然疼痛后，我们评估了遭受慢性、不可预测的轻度应激过程（CUMS，一种抑郁症模型）的大鼠的疼痛行为。模型大鼠的疼痛敏感性较对照组明显增加。与正常大鼠相比，这些大鼠LHb神经元的放电活动显著增加。模型大鼠LHb放电频率高的神经元约73%为疼痛激活神经元（pain-activated neurons， PANS），腹腔注射三环类抗抑郁药氯丙咪嗪可抑制其放电速率。免疫荧光显示，单独接受CUMS、单独接受疼痛刺激和同时接受CUMS和疼痛刺激的大鼠，LHb中c-Fos阳性细胞的百分比均显著增加，但以最后一种刺激的大鼠明显增加。注射氯丙咪嗪可抑制相互作用。LHb损伤可改善抑郁模型大鼠的抑郁样行为和疼痛敏感性。这些表明LHb神经元的过度活跃有助于大鼠的抑郁-疼痛共病。(C) 2016 Elsevier Inc.版权所有。
The interrelation of depression and pain is increasingly coming under scrutiny. Although the lateral habenula (LHb) is widely implicated in the pathogenesis of depression and pain, its role in the interaction of depression and pain remains unknown. Thus, the aim of current study was to investigate the role of LHb in rat depression-pain comorbidity. Single extracellular firing recording and immunofluorescence methods were used to compare firing rates and c-Fos expression of the LHb neurons in normal and model rats. Following subcutaneous injection of formalin into the hind paw to simulate natural pain, we assessed pain behavior in rats subjected to the chronic, unpredictable mild stress procedure (CUMS, a model of depression). Pain sensitivity in the model rats was increased over that of controls. These rats showed a significant increase in the firing activity of LHb neurons compared with normal rats. Significantly, about 73% of neurons with high discharge frequency in LHb of model rats were pain-activated neurons (PANS), and the firing rates of PANs were inhibited by intraperitoneal injection of a tricyclic antidepressant, clomipramine. Immunofluorescence showed that the percentage of c-Fos positive cells in LHb was significantly increased in rats receiving CUMS alone, rats receiving pain stimulation alone, and rats receiving both CUMS and pain stimulation, but especially the last. The interaction effect was inhibited by injection of clomipramine. The LHb lesion can improve both depression-like behavior and pain sensitivity in depression model rats with pain. These suggest that hyperactivity of the LHb neurons contributes to depression-pain comorbidity in rats. (C) 2016 Elsevier Inc. All rights reserved.