A Neural Circuit from Thalamic Paraventricular Nucleus to Central Amygdala for the Facilitation of Neuropathic Pain
A Neural Circuit from Thalamic Paraventricular Nucleus to Central Amygdala for the Facilitation of Neuropathic Pain
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从丘脑室旁核到中央杏仁核的神经回路，用于促进神经性疼痛
DOI：
10.1523/jneurosci.2487-19.2020
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发表时间：
2020-10-07
影响因子：
5.3
通讯作者：
Li, Yun-Qing
中科院分区：
文献类型：
--
作者：
Liang, Shao-Hua;Zhao, Wen-Jun;Li, Yun-Qing
丘脑室旁核（PVT）是丘脑中线核团之一，是许多下行和上行信号通路的重要信号整合部位，调节进食、情绪和药物寻求等多种行为。最近的一项研究表明，PVT涉及急性内脏痛反应，但目前尚不清楚PVT是否在慢性疼痛的中枢处理中发挥关键作用。在这里，我们报告的神经元在后部的PVT（pPVT）和他们的下游通路参与下行伤害性促进关于发展的神经病理性疼痛条件在雄性大鼠。损伤或抑制pPVT神经元可减轻保留神经损伤（SNI）引起的机械性异常性疼痛。SNI大鼠pPVT-中央杏仁核（CeA）投射神经元的兴奋性显著增加。重要的是，pPVT-CeA通路的选择性光遗传学激活在幼稚大鼠中诱导明显的机械超敏反应。此外，我们使用狂犬病病毒（RV）为基础的和细胞类型特异性的逆行跨突触追踪技术来定义一种新的神经元回路，其中vlPAG中的神经元是pPVT-CeA下行易化通路的靶点。我们的数据表明，这种pPVT（Glu+）-CeA-vlPAG（Glu+）回路介导持续性疼痛条件下的下行疼痛易化的中枢机制。
As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVT(Glu+)-CeA-vlPAG(Glu+) circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.