Trigeminal neuropathic pain (TNP) remains a tremendous clinical challenge due to its elusive mechanisms. Previous studies showed that peripheral nerve injury facilitated a selective GABAergic neuronal apoptosis in the superficial dorsal horn and contributed to the development and maintenance of neuropathic pain. It has also demonstrated that downregulation of the anaphase-promoting complex/cyclosome(APC/C) and its coactivator Cdh1 contribute to neuronal apoptosis in diverse neurodegenerative diseases. However, whether APC/C-Cdh1 downregulation could induce GABAergic neuronal apoptosis in trigeminal caudalis nucleus (Vc), and then contribute to the development and maintenance of TNP remains unknown. In this study, we aimed to investigate the role of APC/C-Cdh1 in a TNP rat model and its underlying mechanisms. Our results showed that Cdh1 was primarily distributed in superficial laminae of Vc and significantly downregulated in Vc at day 14 post trigeminal nerve injury. Furthermore, trigerminal nerve injury leads to neuronal apoptosis, especially GABAergic interneurons in the superficial of Vc. Upregulating Cdh1 in Vc ameliorated mechanical allodynia and inhibited GABAergic neuronal apoptosis induced by chronic constriction injury of trigeminal infraorbital nerve (CCI-ION).

中文翻译：

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Cdh1在三叉神经脊髓尾核中的上调通过抑制GABA能神经元凋亡来减轻三叉神经痛。

三叉神经痛（TNP）由于其难以捉摸的机制仍然是一项巨大的临床挑战。先前的研究表明，周围神经损伤促进了浅表背角的选择性GABA能神经元凋亡，并促进了神经性疼痛的发生和维持。还已经证明，促进后期合成的复合物/环体（APC / C）及其共激活因子Cdh1的下调有助于多种神经退行性疾病中的神经元凋亡。然而，APC / C-Cdh1的下调是否会诱导三叉神经尾核（Vc）中的GABA能神经元凋亡，进而有助于TNP的发生和维持尚不清楚。在这项研究中，我们旨在调查APC / C-Cdh1在TNP大鼠模型中的作用及其潜在机制。我们的结果表明，Cdh1主要分布在Vc的表层，在三叉神经损伤后第14天在Vc中明显下调。此外，三叉神经损伤会导致神经元凋亡，尤其是Vc表面的GABA能神经元。Vc中的Cdh1上调改善了机械性异常性疼痛并抑制了三叉神经下眶神经（CCI-ION）的慢性收缩损伤所致的GABA能神经元凋亡。