Background The reactivity enhancement of pain sensitive neurons in the nervous system is a feature of the pathogenesis for neuropathic pain (NP), yet the underlying mechanisms need to be fully understood. In this study, we made an attempt to clarify the NP-related hub genes and signaling pathways so as to provide effective diagnostic and therapeutic methods toward NP. Methods Microarray expression profile GSE30691 including the mRNA-seq data of the spared nerve injury (SNI)-induced NP rats was accessed from the GEO database. Then, genes associated with NP development were screened using differential analysis along with random walk with restart (RWR). GO annotation and KEGG pathway analyses were performed to explore the biological functions and signaling pathways where the genes were activated. Afterward, protein-protein interaction (PPI) analysis and GO analysis were conducted to further identify the hub genes which showed an intimate correlation with NP development. Results Totally 94 genes associated with NP development were screened by differential analysis and RWR analysis, and they were observed to be predominantly enriched in hormone secretion and transport, cAMP signaling pathway and other NP occurrence associated functions and pathways. Thereafter, the 94 genes were subjected to PPI analysis to find the genes much more associated with NP and a functional module composed of 48 genes were obtained. 8 hub genes including C3, C1qb, Ccl2, Cxcl13, Timp1, Fcgr2b, Gal, and Lyz2 were eventually identified after further association and functional enrichment analyses, and the expression of these 8 genes were all higher in SNI rats by comparison with those in Sham rats. Conclusion Based on the data collected from GEO database, this study discovered 8 hub genes that were closely related to NP occurrence and development, which help to provide potent theoretical basis for NP treatment.

中文翻译：

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鉴定与神经损伤引起的神经性疼痛相关的中枢基因

背景 神经系统中疼痛敏感神经元的反应性增强是神经性疼痛（NP）发病机制的一个特征，但其潜在机制需要充分了解。在本研究中，我们试图阐明与NP相关的中枢基因和信号通路，以期为NP提供有效的诊断和治疗方法。方法 从 GEO 数据库访问微阵列表达谱 GSE30691，包括幸免神经损伤 (SNI) 诱导的 NP 大鼠的 mRNA-seq 数据。然后，使用差异分析以及带重启的随机游走 (RWR) 筛选与 NP 发育相关的基因。进行GO注释和KEGG通路分析以探索基因被激活的生物学功能和信号通路。之后，进行蛋白质-蛋白质相互作用（PPI）分析和GO分析以进一步鉴定与NP发育密切相关的中心基因。结果通过差异分析和RWR分析共筛选出94个与NP发生相关的基因，观察到它们主要富集在激素分泌与转运、cAMP信号通路等与NP发生相关的功能和通路中。此后，对94个基因进行PPI分析，寻找与NP关联度更高的基因，得到由48个基因组成的功能模块。经过进一步的关联和功能富集分析，最终确定了包括 C3、C1qb、Ccl2、Cxcl13、Timp1、Fcgr2b、Gal 和 Lyz2 在内的 8 个中枢基因，与Sham大鼠相比，这8个基因在SNI大鼠中的表达均较高。结论 本研究基于GEO数据库收集的数据，发现了8个与NP发生、发展密切相关的枢纽基因，为NP治疗提供有力的理论依据。