114027
论文已发表
注册即可获取德孚的最新动态
IF 收录期刊
- 3.4 Breast Cancer (Dove Med Press)
- 3.2 Clin Epidemiol
- 2.6 Cancer Manag Res
- 2.9 Infect Drug Resist
- 3.7 Clin Interv Aging
- 5.1 Drug Des Dev Ther
- 3.1 Int J Chronic Obstr
- 6.6 Int J Nanomed
- 2.6 Int J Women's Health
- 2.9 Neuropsych Dis Treat
- 2.8 OncoTargets Ther
- 2.0 Patient Prefer Adher
- 2.2 Ther Clin Risk Manag
- 2.5 J Pain Res
- 3.0 Diabet Metab Synd Ob
- 3.2 Psychol Res Behav Ma
- 3.4 Nat Sci Sleep
- 1.8 Pharmgenomics Pers Med
- 2.0 Risk Manag Healthc Policy
- 4.1 J Inflamm Res
- 2.0 Int J Gen Med
- 3.4 J Hepatocell Carcinoma
- 3.0 J Asthma Allergy
- 2.2 Clin Cosmet Investig Dermatol
- 2.4 J Multidiscip Healthc
已发表论文
在坐骨神经损伤所致神经病理性疼痛雄性大鼠中鉴定出的细胞焦亡相关基因
Authors Li W , Hu Z, Lin P, He L, Liu R
Received 10 October 2025
Accepted for publication 17 December 2025
Published 23 December 2025 Volume 2025:18 Pages 7029—7041
DOI https://doi.org/10.2147/JPR.S568630
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Houman Danesh
Wangyu Li,1,2,* Zhouting Hu,3,* Peng Lin,1,2,* Long He,1,2 Rongguo Liu1,2
1Department of Painology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Painology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Anesthesiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Long He, Email 1038370096@qq.com Rongguo Liu, Email 9201151029@fjmu.edu.cn
Purpose: Pyroptosis, a programmed inflammatory cell death mechanism, plays a significant role in neuropathic pain (NP) pathogenesis. However, the specific pyroptosis-related genes (PRGs) driving NP development remain poorly understood. This study employs systematic approaches to identify and validate PRGs, aiming to delineate their mechanistic contributions to NP progression.
Methods: To elucidate pyroptosis-related genes (PRGs) in neuropathic pain pathogenesis, we first performed integrated bioinformatics analysis of the GSE236754 dataset, revealing differentially expressed PRGs in the spinal cord dorsal horn of spared nerve injury (SNI) rats. Subsequent functional enrichment analyses coupled with protein-protein interaction network construction delineated pathway convergences among identified PRGs. Experimental validation utilizing SNI rat model, Western blot and immunofluorescence quantification confirmed protein expression patterns, and immunofluorescence mapping determined cellular localization collectively. Statistical analyses via ANOVA method.
Results: Bioinformatics screening identified 11 candidate PRGs in the SNI model, particularly highlighting Nlrc4 and Nlrp3 as the most upregulated targets. Gene Ontology (GO) analysis demonstrated significant enrichment in three domains, pyroptosis regulation, inflammasome complex assembly, and cysteine-type endopeptidase activity associated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis specifically identified the “NOD-like receptor signaling pathway” as significantly enriched. Gene Set Enrichment Analysis (GSEA) further corroborated these findings. Behavioral quantification showed progressive mechanical hypersensitivity, with mechanical pain and cold pain reaching maximal sensitivity at day 7 post-injury (p< 0.001). Western blot detected synchronized elevation of NLRP3 and NLRC4 inflammasome components and downstream effectors across the observation window (all p< 0.05). Immunofluorescence analysis demonstrated a time-dependent increase in the expression of GSDMD-N, the pyroptotic-executing protein, a trend consistent with the findings from behavioral tests and Western blot analysis (p< 0.05). And cellular localization analysis revealed neuron-predominant accumulation of GSDMD-N.
Conclusion: We identified 11 potential biomarkers for NP. Our data conclusively show that SNI induced NLRP3/NLRC4 inflammasome activation and neuronal pyroptosis in the rat spinal cord.
Keywords: neuropathic pain, pyroptosis, bioinformatics, causal relationship, inflammasome
1Department of Painology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Department of Painology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Anesthesiology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Long He, Email 1038370096@qq.com Rongguo Liu, Email 9201151029@fjmu.edu.cn
Purpose: Pyroptosis, a programmed inflammatory cell death mechanism, plays a significant role in neuropathic pain (NP) pathogenesis. However, the specific pyroptosis-related genes (PRGs) driving NP development remain poorly understood. This study employs systematic approaches to identify and validate PRGs, aiming to delineate their mechanistic contributions to NP progression.
Methods: To elucidate pyroptosis-related genes (PRGs) in neuropathic pain pathogenesis, we first performed integrated bioinformatics analysis of the GSE236754 dataset, revealing differentially expressed PRGs in the spinal cord dorsal horn of spared nerve injury (SNI) rats. Subsequent functional enrichment analyses coupled with protein-protein interaction network construction delineated pathway convergences among identified PRGs. Experimental validation utilizing SNI rat model, Western blot and immunofluorescence quantification confirmed protein expression patterns, and immunofluorescence mapping determined cellular localization collectively. Statistical analyses via ANOVA method.
Results: Bioinformatics screening identified 11 candidate PRGs in the SNI model, particularly highlighting Nlrc4 and Nlrp3 as the most upregulated targets. Gene Ontology (GO) analysis demonstrated significant enrichment in three domains, pyroptosis regulation, inflammasome complex assembly, and cysteine-type endopeptidase activity associated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis specifically identified the “NOD-like receptor signaling pathway” as significantly enriched. Gene Set Enrichment Analysis (GSEA) further corroborated these findings. Behavioral quantification showed progressive mechanical hypersensitivity, with mechanical pain and cold pain reaching maximal sensitivity at day 7 post-injury (p< 0.001). Western blot detected synchronized elevation of NLRP3 and NLRC4 inflammasome components and downstream effectors across the observation window (all p< 0.05). Immunofluorescence analysis demonstrated a time-dependent increase in the expression of GSDMD-N, the pyroptotic-executing protein, a trend consistent with the findings from behavioral tests and Western blot analysis (p< 0.05). And cellular localization analysis revealed neuron-predominant accumulation of GSDMD-N.
Conclusion: We identified 11 potential biomarkers for NP. Our data conclusively show that SNI induced NLRP3/NLRC4 inflammasome activation and neuronal pyroptosis in the rat spinal cord.
Keywords: neuropathic pain, pyroptosis, bioinformatics, causal relationship, inflammasome