Abstract
Objective Neuropathic pain (NP) is a type of intractable chronic pain with complicated etiology. The exact molecular mechanism underlying NP remains unclear. In this study, we searched for molecular biomarkers of NP. Methods Differentially expressed genes (DEGs) were predicted by analyzing three NP-related microarray datasets in Gene Expression Omnibus with robust rank aggregation. A weighted gene coexpression network analysis was conducted to construct a network of differentially expressed genes, followed by the evaluation of correlations between gene sets and the determination of hub genes. The candidate genes from the key module were identified using a gene set enrichment analysis. Results In total, 353 upregulated and 383 downregulated genes were obtained, among which five hub genes were determined to be related to pain phenotypes. Reverse transcription-quantitative polymerase chain reaction was performed to verify the expression of these hub genes in the dorsal root ganglia of rats with spared nerve injury, which revealed the decreased expression of EMC4. Hence, EMC4 was defined as a biomarker for NP development. Conclusions The results of this study form a basis for further research into the mechanism of NP development and are expected to aid in the development of novel therapeutic strategies.
Highlights
As a type of chronic pain with complex etiology, neuropathic pain (NP) is characterized by hyperalgesia, numbness, and allodynia [1]
Evidence shows that genetic variations in DRGs are related to pain phenotypes [5]. erefore, it is of importance to analyze gene expression changes in the DRGs after peripheral nerve injury for the understanding of the molecular mechanism underlying NP, which may contribute to the development of an effective therapeutic regimen
We proposed a research hypothesis that potential core genes for NP could be identified by differentially expressed genes (DEGs) and replicated in animal models. is work was conducted to detect the expression of DEGs and determine their reproducibility in an animal model of NP
Summary
Neuropathic pain (NP) is a type of intractable chronic pain with complicated etiology. e exact molecular mechanism underlying NP remains unclear. We searched for molecular biomarkers of NP. Expressed genes (DEGs) were predicted by analyzing three NP-related microarray datasets in Gene Expression Omnibus with robust rank aggregation. A weighted gene coexpression network analysis was conducted to construct a network of differentially expressed genes, followed by the evaluation of correlations between gene sets and the determination of hub genes. E candidate genes from the key module were identified using a gene set enrichment analysis. 353 upregulated and 383 downregulated genes were obtained, among which five hub genes were determined to be related to pain phenotypes. E results of this study form a basis for further research into the mechanism of NP development and are expected to aid in the development of novel therapeutic strategies Conclusions. e results of this study form a basis for further research into the mechanism of NP development and are expected to aid in the development of novel therapeutic strategies
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