Abstract
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.
Highlights
Neuropathic pain refers to chronic pain originating from neurological pathology, and it affects approximately 7–10% of the global population [1, 2]
The microarray data GSE30691 deposited in the NCBI Gene Expression Omnibus (GEO) database by Costigan et al [12], which were generated on the GPL85 [RG_U34A] Affymetrix Rat Genome U34 Array platform, was downloaded
The unions of differentially expressed genes (DEGs) that had the same expression change tendency at three time points were analyzed, and a total of 306 DEGs were obtained for subsequent analysis
Summary
Neuropathic pain refers to chronic pain originating from neurological pathology, and it affects approximately 7–10% of the global population [1, 2]. It is characterized by spontaneous hyperalgesia, dysesthesia, and allodynia [3, 4]. The pathogenesis of neuropathic pain is complex, and elucidation of specific molecular alterations helps understand the mechanisms involved in neuropathic pain development. Since the development of bioinformatics, massive microarray data have been used to extensively investigate the candidate molecules associated with SNI-induced neuropathic pain and help identify potential targets for disease diagnosis and treatment.
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