本研究旨在探讨长链非编码RNA小核仁RNA宿主基因5(SNHG5)在慢性缩窄性损伤(CCI)诱导的神经病理性疼痛(NP)中的作用及机制。使用CCI方法建立NP大鼠模型,并通过爪退缩阈值(PWT)和爪退缩潜伏期(PWL)评估NP严重程度。在大鼠背根神经节中定量SNHG5,CDK9和SCN9A的表达,除了检测细胞凋亡,病理变化,神经元数,以及Nav1.7和裂解的caspase-3与NeuN的共定位。在ND7/23细胞中,细胞凋亡和乳酸脱氢酶浓度进行评估,以及SNHG5、CDK9和SCN9A之间的关系。在CCI处理的大鼠的背根神经节中,SNHG5和SCN9A上调,SNHG5的下调抑制了SCN9A的表达,增加了PWT和PWL,阻断神经炎症和神经元凋亡,缓解NP。机械上,SNHG5招募CDK9以增强SCN9A编码的Nav1.7表达并促进外周神经元凋亡和损伤。此外,SCN9A过表达消除了SNHG5缺乏对CCI大鼠NP和神经元丢失的缓解作用。总之,SNHG5通过募集CDK9促进SCN9A编码的Nav1.7表达,从而促进脊髓神经损伤后的神经元丢失和NP,这可能为NP的管理提供一个有希望的目标。
This study aims to explore the functions and mechanisms of long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) in chronic constriction injury (CCI)-induced neuropathic pain (NP). An NP rat model was established using the CCI method and the NP severity was evaluated by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The expression of SNHG5, CDK9, and
SCN9A was quantified in rat dorsal root ganglion, in addition to the detections of apoptosis, pathological changes, neuron number, and the co-localization of Nav1.7 and cleaved caspase-3 with NeuN. In ND7/23 cells, the apoptosis and lactate dehydrogenase concentration were assessed, as well as the relationship between SNHG5, CDK9, and SCN9A. In the dorsal root ganglion of CCI-treated rats, SNHG5 and
SCN9A were upregulated and downregulation of SNHG5 suppressed
SCN9A expression, increased the PWT and PWL, blocked neuroinflammation and neuronal apoptosis, and alleviated NP. Mechanistically, SNHG5 recruited CDK9 to enhance
SCN9A-encoded Nav1.7 expression and promoted peripheral neuronal apoptosis and injury. In addition, SCN9A overexpression nullified the alleviative effects of SNHG5 deficiency on NP and neuron loss in CCI rats. In conclusion, SNHG5 promotes
SCN9A-encoded Nav1.7 expression by recruiting CDK9, thereby facilitating neuron loss and NP after spinal nerve injury, which may offer a promising target for the management of NP.