Activation of ventrolateral orbital cortex improves mouse neuropathic pain-induced anxiodepression
Activation of ventrolateral orbital cortex improves mouse neuropathic pain-induced anxiodepression
复制标题
腹外侧眶皮层的激活可改善小鼠神经性疼痛引起的抗氧化抑郁。
DOI：
10.1172/jci.insight.133625
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发表时间：
2020-10-02
期刊：
影响因子：
8
通讯作者：
Zhang, Yu-Qiu
中科院分区：
文献类型：
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作者：
Sheng, Hai-Yan;Lv, Su-Su;Zhang, Yu-Qiu
在患有神经性疼痛的患者中经常观察到抑郁和焦虑。其潜在机制尚不清楚。腹外侧眶皮层（VLO）在啮齿类动物抗抑郁作用中的作用引起了人们的极大兴趣。在本研究中，我们进一步研究了VLO在眶下神经慢性压迫性损伤诱导的三叉神经痛（TN）小鼠模型中神经病理性疼痛的焦虑抑郁后果中的作用。采用高架十字迷宫、旷场、强迫游泳、悬尾和蔗糖偏好试验评价焦虑抑郁样行为。结果表明，化学发生激活双侧VLO神经元，尤其是CaMK 2A（+）锥体神经元，阻断TN诱导的焦虑抑郁样行为。VGLUT 2（+）的化学遗传学和光遗传学激活或VGAT（+）VLO神经元的抑制足以在TN小鼠中产生抗焦虑抑郁作用。药理学激活的D1样受体（D1 Rs），但不D2 Rs的VLO显着减轻TN诱导的抑郁样行为。电生理记录显示神经病理性疼痛后VLO兴奋性神经元的兴奋性降低。此外，丘脑中央下核-VLO（Sm-VLO）投射的激活模拟了VLO兴奋的抗焦虑抑郁作用。相反，VLO-导水管周围灰质（PAG）投射的激活对TN诱导的焦虑抑郁行为没有影响。这项研究提供了一个潜在的新的机制为基础的治疗策略的焦虑抑郁的神经性疼痛的后果。
Depression and anxiety are frequently observed in patients suffering from neuropathic pain. The underlying mechanisms remained unclear. The ventrolateral orbital cortex (VLO) has attracted considerable interest in its role in antidepressive effect in rodents. In the present study, we further investigated the role of the VLO in the anxiodepressive consequences of neuropathic pain in a chronic constriction injury of infraorbital nerve-induced trigeminal neuralgia (TN) mouse model. Elevated plus maze, open field, forced swimming, tail suspension, and sucrose preference tests were used to evaluate anxiodepressive-like behaviors. The results show that chemogenetic activation of bilateral VLO neurons, especially CaMK2A(+) pyramidal neurons, blocked the TN-induced anxiodepressive-like behaviors. Chemogenetic and optogenetic activation of VGLUT2(+) or inhibition of VGAT(+) VLO neurons was sufficient to produce an antianxiodepressive effect in TN mice. Pharmacological activation of D1-like receptors (D1Rs) but not D2Rs in the VLO significantly alleviated TN-induced depressive-like behaviors. Electrophysiological recordings revealed a decreased excitability of VLO excitatory neurons following neuropathic pain. Furthermore, activation of submedius thalamic nucleus-VLO (Sm-VLO) projection mimicked the antianxiodepressive effect of VLO excitation. Conversely, activation of VLO-periaqueductal gray matter (PAG) projection had no effect on TN-induced anxiodepressive behaviors. This study provides a potentially novel mechanism-based therapeutic strategy for the anxiodepressive consequences of neuropathic pain.