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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis
Yaling Lou1, Xuting Xu2, Ronghua Wang1
1Department of Clinical Pharmacy, Huzhou Central Hospital (The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University), Huzhou, People's Republic of China.
Background:
The mechanism of Chemotherapy-induced neuropathic pain (NP) remains obscure. This study was aimed to uncover the key genes as well as protein networks that contribute to Oxaliplatin-induced NP.
Material/Methods:
Oxaliplatin frequently results in a type of Chemotherapy-induced NP that is marked by heightened sensitivity to mechanical and cold stimuli, which can lead to intolerance and discontinuation of medication. We investigated whether these different etiologies lead to similar pathological outcomes by targeting shared genetic targets or signaling pathways. Gene expression data were obtained from the Gene Expression Comprehensive Database (GEO) for GSE38038 (representing differential expression in the spinal nerve ligation model rats) and GSE126773 (representing differential expression among the Oxaliplatin-induced NP model rats). Differential gene expression analysis was performed using GEO2R.
Results:
Protein-protein interaction (PPI) analysis identified 260 co-differentially expressed genes (co-DEGs). Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed three shared pathways involved in both models: Kaposi sarcoma-associated herpesvirus (KSHV) infection, Epstein-Barr virus (EBV) infection, and AGE-RAGE signaling pathway in diabetic complications. Further bioinformatics analysis highlighted eight significantly up-regulated genes in the NP group: Mapk14, Icam1, Cd44, IL6, Cxcr4, Stat1, Casp3 and Fgf2. Our results suggest that immune dysfunction, inflammation-related factors or regulating inflammation factors may also be related to Oxaliplatin-induced NP. Additionally, we analyzed a dataset (GSE145222) involving chronic compression of DRGs (CCD) and control groups. CCD model is a classic model for studying NP. We assessed these hub genes' expression levels. In contrast with the control groups, the hub genes were up-regulated in CCD groups, the difference was statistically significant, except Stat1.
Conclusion:
Our research significantly contributes to elucidating the mechanisms underlying the occurrence as well as the progression of Oxaliplatin-induced NP. We have identified crucial genes and signaling pathways associated with this condition.
Insights
This study identifies key genes and pathways involved in Oxaliplatin-induced neuropathic pain (NP), revealing potential targets for managing chemotherapy side effects and improving patient treatment outcomes.
Area of Science:
- Neuroscience
- Genomics
- Pharmacology
Background:
- Chemotherapy-induced neuropathic pain (NP) mechanisms are not fully understood.
- Oxaliplatin commonly causes NP with hypersensitivity to cold and mechanical stimuli.
- This hypersensitivity can lead to treatment discontinuation.
Purpose of the Study:
- To identify key genes and protein networks contributing to Oxaliplatin-induced NP.
- To investigate shared pathological outcomes and genetic targets between different NP etiologies.
- To elucidate the underlying mechanisms of Oxaliplatin-induced NP.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) datasets (GSE38038, GSE126773) for differential gene expression analysis via GEO2R.
- Performed protein-protein interaction (PPI) analysis to identify co-differentially expressed genes (co-DEGs).
- Conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and analyzed a chronic compression of DRGs (CCD) dataset (GSE145222).
Main Results:
- Identified 260 co-DEGs and three shared pathways (KSHV infection, EBV infection, AGE-RAGE signaling).
- Eight significantly up-regulated genes in NP models include Mapk14, Icam1, Cd44, IL6, Cxcr4, Stat1, Casp3, and Fgf2.
- Hub genes were up-regulated in both Oxaliplatin-induced NP and CCD models, suggesting shared NP mechanisms.
Conclusions:
- This research elucidates key genes and signaling pathways in Oxaliplatin-induced NP.
- Findings contribute to understanding the occurrence and progression of chemotherapy-induced NP.
- Identified crucial molecular targets for potential therapeutic interventions.
