Purpose. The study was aimed at elucidating the molecular mechanism underlying neuropathic pain induced by spared nerve injury (SNI). Methods. The microarray data of GSE30691 were downloaded from the Gene Expression Omnibus database, including sciatic nerve lesion samples at 3, 7, 21, and 40 days after SNI and sham control samples at 3, 7, and 21 days. Differential analysis along with Mfuzz clustering analysis was performed to screen crucial clusters and cluster genes. Subsequently, comprehensive bioinformatic analyses were performed, including functional enrichment analysis, protein-protein interaction (PPI) network and module analysis, and transcription factor- (TF-) gene and miRNA-target interaction predictions. Moreover, the screened differentially expressed genes (DEGs) were corroborated using two other microarray datasets. Results. Three clusters with different change trends over time after SNI were obtained. Protein kinase CAMP-activated catalytic subunit beta (Prkacb), complement C3 (C3), and activating transcription factor 3 (Atf3) were hub nodes in the PPI network, and fibroblast growth factor 9 (Fgf9) was found to interact with more TFs. Prkacb and Fgf9 were significantly enriched in the MAPK signaling pathway. Moreover, rno-miR-3583-5p was targeted by Fgf9, and rno-miR-1912-3p was targeted by neuregulin 1 (Nrg1). Key genes like Nrg1 and Fgf9 in cluster 1, Timp1 in cluster 2, and Atf3 and C3 in cluster 3 were screened out after corroborating microarray data with other microarray data. Conclusions. Key pathways like the MAPK signaling pathway and crucial genes like Prkacb, Nrg1, Fgf9, Timp1, C3, and Atf3 may contribute to SNI-induced neuropathic pain development in rats.

中文翻译：

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稀有神经损伤引起的神经性疼痛相关的关键基因和途径分析

目的。这项研究旨在阐明由幸免的神经损伤（SNI）引起的神经性疼痛的分子机制。方法。GSE30691的微阵列数据是从Gene Expression Omnibus数据库下载的，包括SNI后3、7、21和40天的坐骨神经病变样品和3、7、21天的假对照样品。进行了差异分析和Mfuzz聚类分析，以筛选关键的簇和簇基因。随后，进行了全面的生物信息学分析，包括功能富集分析，蛋白质-蛋白质相互作用（PPI）网络和模块分析，以及转录因子-（TF-）基因和miRNA-靶标相互作用的预测。此外，使用其他两个微阵列数据集证实了筛选的差异表达基因（DEG）。结果。获得了SNI之后随时间变化趋势不同的三个聚类。蛋白激酶CAMP激活的催化亚基beta（Prkacb），补体C3（C3）和激活的转录因子3（Atf3）是PPI网络中的枢纽节点，并且发现成纤维细胞生长因子9（Fgf9）与更多TF相互作用。Prkacb和Fgf9在MAPK信号通路中显着富集。此外，RNO-MIR-3583-5p通过靶向Fgf9基因，和RNO-MIR-1912-3p由神经调节蛋白1（靶向NRG1）。关键基因如簇1中的Nrg1和Fgf9，簇2中的Timp1以及Atf3和C3在将微阵列数据与其他微阵列数据相确证后，筛选出簇3中的H2O。结论。MAPK信号传导途径等关键途径以及Prkacb，Nrg1，Fgf9，Timp1，C3和Atf3等关键基因可能有助于SNI诱导大鼠神经性疼痛的发展。