Abstract

BackgroundThe 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.MethodsMicroarray 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.ResultsTotally 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.ConclusionBased 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.

Highlights

  • Pain is a survival mechanism that can act as a warning sign of ongoing or impending tissue damage

  • Totally 94 genes associated with Neuropathic pain (NP) development were screened by differential analysis and random walk with restart (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 protein-protein interaction (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 spared nerve injury (SNI) rats by comparison with those in Sham rats

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Summary

Introduction

Pain is a survival mechanism that can act as a warning sign of ongoing or impending tissue damage. The specific mechanisms underlying NP remain elusive and there is still a lack of the effective therapeutic methods. It is urgent to further clarify the underlying mechanisms toward NP and exploit the relevant genes and signaling pathways, so as to provide theoretical basis and new ideas for future treatment. 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.

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