Systematic analysis of critical genes and pathways identified a signature of neuropathic pain after spinal cord injury. (27th May 2022)

• Record Type: Journal Article
• Authors: Li, Zefu; Bai, Huiying; Zhang, Ruoyu; Chen, Bohan; Wang, Junmin; Xue, Bohan; Ren, Xiuhua; Wang, Jiarui; Jia, Yanjie; Zang, Weidong; Wang, Jian; Chen, Xuemei
• Is Part Of: European journal of neuroscience. Volume 56:Number 2(2022)
• Page Start: 3991
• Page End: 4008
• Publication Date: 2022-05-27
• Subjects: natural language processing analysis -- neuroinflammation -- neuropathic pain -- spinal cord injury -- toll‐like receptor 4; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15693
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Spinal cord injury (SCI) damages sensory systems, producing chronic neuropathic pain that is resistant to medical treatment. The specific mechanisms underlying SCI‐induced neuropathic pain (SCI‐NP) remain unclear, and protein biomarkers have not yet been integrated into diagnostic screening. To better understand the host molecular pathways involved in SCI‐NP, we used the bioinformatics method, the PubMed database and bioinformatics methods to identify target genes and their associated pathways. We reviewed 2504 articles on the regulation of SCI‐NP and used the text mining of PubMed database abstracts to determine associations among 12 pathways and networks. Based on this method, we identified two central genes in SCI‐NP: interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α). Adult male Sprague–Dawley rats were used to build the SCI‐NP models. The threshold for paw withdrawal was significantly reduced in the SCI group, and TLR4 was activated in microglia after SCI. Enzyme‐linked immunosorbent assay（ELISA) analysis of TNF‐α and IL‐6 levels was significantly higher in the SCI group than in the sham group. Western blot showed that expressions of the TLR4/MyD88/NF‐κB inflammatory pathway protein increased dramatically in the SCI group. Using the TLR4 inhibitor TAK‐242, the pain threshold and expressions of inflammatory factors and proteins of the proteins of the inflammatory signal pathway were reversed, TLR4 in microglia was suppressed, suggesting that SCI‐NP was related to neuroinflammation mediated by the TLR4 signalling pathway. In conclusion, we found that TNF‐α and IL‐6 were the neuroinflammation‐related genes involved in SCI‐NP that can be alleviated by inhibiting the inflammatory pathway upstream of the TLR4/MyD88/NF‐κB inflammatory pathway. Abstract : Interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) are critical genes in spinal cord injury neuropathic pain after systematic analysis, and neuropathic pain and neuroinflammation caused by IL‐6 and TNF‐α are alleviated by inhibiting the inflammatory pathway TLR4/MyD88/NF‐κB inflammatory pathway.