Department of Anesthesiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University School of Medicine, Nanjing, Jiangsu 210008, P.R. China.
Mol Med Rep. 2018 May;17(5):6371-6378. doi: 10.3892/mmr.2018.8718. Epub 2018 Mar 9.
Neuropathic pain is a chronic pain state associated with multiple etiologies that results in considerable social and economic burden. The identification of key genes associated with neuropathic pain is important for the development of novel therapies. Therefore, the present study downloaded the gene expression profile GSE15041 from the Gene Expression Omnibus database. The unverified gene chip was removed and the microarray data was normalized following quality control. The limma package in R was used to screen the differentially expressed genes (DEGs), followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Furthermore, a protein‑protein interaction (PPI) network based on the identified DEGs was constructed to select hub proteins, and reverse transcription‑quantitative polymerase chain reaction was performed to detect the expression of these proteins in a mouse model of neuropathic pain. In total, 86 common DEGs were identified. DEGs were significantly enriched in ̔extracellular space̓ and KEGG pathway enrichment analysis demonstrated that the DEGs were significantly enriched in inflammatory diseases and the mitogen‑activated protein kinase signaling pathway. The PPI network consisted of 27 nodes (proteins) and 47 PPI edges (interactions). Interleukin (IL)‑6, transcription factor AP‑1 (c‑Jun) and urikinase‑type plasminogen activator (Plau) were identified as hub proteins and key genes in neuropathic pain. The mRNA expression of these hub proteins was significantly increased in the neuropathic pain model, compared with the sham group. IL‑6, c‑Jun, and Plau may be involved in development of neuropathic pain and further research investigating the exact role of these key genes is required.
神经病理性疼痛是一种与多种病因相关的慢性疼痛状态，会给社会和经济带来巨大负担。鉴定与神经病理性疼痛相关的关键基因对于开发新的治疗方法很重要。因此，本研究从基因表达综合数据库中下载了基因表达谱 GSE15041。去除未经证实的基因芯片，并在质量控制后对微阵列数据进行标准化。使用 R 中的 limma 包筛选差异表达基因（DEGs），然后进行基因本体论和京都基因与基因组百科全书（KEGG）通路富集分析。此外，基于鉴定的 DEGs 构建蛋白质-蛋白质相互作用（PPI）网络，选择枢纽蛋白，并进行逆转录-定量聚合酶链反应检测神经病理性疼痛小鼠模型中这些蛋白的表达。共鉴定出 86 个共同的 DEGs。DEGs 在“细胞外空间”中显著富集，KEGG 通路富集分析表明，DEGs 在炎症性疾病和丝裂原激活蛋白激酶信号通路中显著富集。PPI 网络由 27 个节点（蛋白）和 47 个 PPI 边（相互作用）组成。白细胞介素（IL）-6、转录因子 AP-1（c-Jun）和尿激酶型纤溶酶原激活物（Plau）被鉴定为神经病理性疼痛的枢纽蛋白和关键基因。与假手术组相比，这些枢纽蛋白在神经病理性疼痛模型中的 mRNA 表达显著增加。IL-6、c-Jun 和 Plau 可能参与神经病理性疼痛的发展，需要进一步研究这些关键基因的确切作用。
