Systematic analysis of critical genes and pathways identified a signature of neuropathic pain after spinal cord injury

Li, Zefu; Bai, Huiying; Zhang, Ruoyu; Chen, Bohan; Wang, Junmin; Xue, Bohan; Ren, Xiuhua; Wang, Jiarui; Jia, Yanjie; Zang, Weidong; Wang, Jian; Chen, Xuemei

doi:10.1111/ejn.15693

Cited by 4 publications

(6 citation statements)

References 64 publications

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“…In addition, previous studies have also performed bioinformatics analysis of key signaling pathways in SCI (J. H. Li et al., 2020 ). A study proposed by (Z. Li et al., 2022 ) noted that the TLR4/MyD88/NF‐κB inflammatory pathway was activated in SCI through bioinformatics analysis, which further supports our findings. The WGCNA method was used for the construction of a co‐expression network, and modules with clinical features were determined (Tian et al., 2020 ).…”

Section: Discussionsupporting

confidence: 91%

Identification of age‐specific biomarkers of spinal cord injury: A bioinformatics analysis of young and aged mice models

Miao,

Su,

Cheng

2023

Brain and Behavior

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BackgroundSpinal cord injury (SCI) is a debilitating event that often results in long‐term physical damage, disability, and a significant impact on a patient's quality of life. Past research has noted an age‐dependent decline in regeneration post‐SCI. This study seeks to identify potential biomarkers and enriched pathways in young and aged SCI mouse models.MethodsWe retrieved the microarray data of spinal cord samples from SCI mice and control mice from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the R software and the Linear Models for Microarray Data (limma) package. The Gene Set Enrichment Analysis (GSEA) determined enrichment differences among gene sets. The Weighted Gene Co‐expression Network Analysis (WGCNA) pinpointed clinically significant modules and hub genes in SCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was employed to uncover significantly related pathways of crucial genes in SCI.ResultsWe found 2560 DEGs in the young SCI group, comprised of 1733 upregulated RNAs and 827 downregulated RNAs. In the aged SCI group, 3048 DEGs were revealed including 1856 upregulated and 1192 downregulated genes. The GSEA revealed 12 enriched signaling pathways in the young SCI group, such as IL6/JAK/STAT3 signaling, interferon alpha response, and interferon gamma response, and 21 signaling pathways in the aged SCI group such as IL6/JAK/STAT3 signaling, E2F targets, and angiogenesis‐related pathways. The WGCNA identified the turquoise module as significantly associated with the clinical traits of both young and aged SCI, and revealed 3181 hub genes. Ultimately, 1858 significant genes in SCI were found, with associated signaling pathways including epithelial‐mesenchymal transition (EMT), interferon gamma response, and KARS signaling.ConclusionOur study explored the RNA expression patterns and enriched signaling pathways in young and aged SCI mice. These findings may provide potential biomarkers for targeted SCI therapy.

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Section: Discussionsupporting

confidence: 91%

Identification of age‐specific biomarkers of spinal cord injury: A bioinformatics analysis of young and aged mice models

Miao,

Su,

Cheng

2023

Brain and Behavior

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“…The defining characteristic of SCI is the development of cysts, which are closely linked to the TLR/myeloid differentiation primary response gene 88 (MyD88) signaling route in astrocytes. These astrocytes exhibit a persistent apoptotic response to necrosis via the TLR4/Myd88 signaling pathway ( Li et al, 2022 ). The inhibitory effect on axonal regeneration during recovery is typically attributed to the presence of CSPGs that are generated by astrocytes in glial scarring.…”

Section: Pathophysiological Process Of Scimentioning

confidence: 99%

Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

Gao,

Wang,

et al. 2024

Front. Cell. Neurosci.

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Spinal cord injury (SCI) disrupts nerve pathways and affects sensory, motor, and autonomic function. There is currently no effective treatment for SCI. SCI occurs within three temporal periods: acute, subacute, and chronic. In each period there are different alterations in the cells, inflammatory factors, and signaling pathways within the spinal cord. Many biomaterials have been investigated in the treatment of SCI, including hydrogels and fiber scaffolds, and some progress has been made in the treatment of SCI using multiple materials. However, there are limitations when using individual biomaterials in SCI treatment, and these limitations can be significantly improved by combining treatments with stem cells. In order to better understand SCI and to investigate new strategies for its treatment, several combination therapies that include materials combined with cells, drugs, cytokines, etc. are summarized in the current review.

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“…Moreover, increased NF-κB activity has been demonstrated not only in the DRGs but also in the spinal cord of various neuropathic pain model animals [21,22,44,182,184,190,191]. Recently, it was also shown that the levels of the pronociceptive factors TNFα and IL-6, which are involved in neuropathic pain development after spinal cord injury, can be decreased by inhibiting the TLR4/MyD88/NF-κB pathway [192]. Similarly, after sciatic nerve injury, the selective inhibition of NF-κB reduces hypersensitivity, which has been shown to be associated with beneficial effects on the levels of the pronociceptive factors IL-6 and iNOS [182].…”

Section: Nf-κb and Neuropathic Painmentioning

confidence: 99%

Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics

Ciapała,

Mika

2023

Pharmaceuticals

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Neuropathic pain is a complex and debilitating condition that affects millions of people worldwide. Unlike acute pain, which is short-term and starts suddenly in response to an injury, neuropathic pain arises from somatosensory nervous system damage or disease, is usually chronic, and makes every day functioning difficult, substantially reducing quality of life. The main reason for the lack of effective pharmacotherapies for neuropathic pain is its diverse etiology and the complex, still poorly understood, pathophysiological mechanism of its progression. Numerous experimental studies, including ours, conducted over the last several decades have shown that the development of neuropathic pain is based on disturbances in cell activity, imbalances in the production of pronociceptive factors, and changes in signaling pathways such as p38MAPK, ERK, JNK, NF-κB, PI3K, and NRF2, which could become important targets for pharmacotherapy in the future. Despite the availability of many different analgesics, relieving neuropathic pain is still extremely difficult and requires a multidirectional, individual approach. We would like to point out that an increasing amount of data indicates that nonselective compounds directed at more than one molecular target exert promising analgesic effects. In our review, we characterize four substances (minocycline, astaxanthin, fisetin, and peimine) with analgesic properties that result from a wide spectrum of actions, including the modulation of MAPKs and other factors. We would like to draw attention to these selected substances since, in preclinical studies, they show suitable analgesic properties in models of neuropathy of various etiologies, and, importantly, some are already used as dietary supplements; for example, astaxanthin and fisetin protect against oxidative stress and have anti-inflammatory properties. It is worth emphasizing that the results of behavioral tests also indicate their usefulness when combined with opioids, the effectiveness of which decreases when neuropathy develops. Moreover, these substances appear to have additional, beneficial properties for the treatment of diseases that frequently co-occur with neuropathic pain. Therefore, these substances provide hope for the development of modern pharmacological tools to not only treat symptoms but also restore the proper functioning of the human body.

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Systematic analysis of critical genes and pathways identified a signature of neuropathic pain after spinal cord injury

Cited by 4 publications

References 64 publications

Identification of age‐specific biomarkers of spinal cord injury: A bioinformatics analysis of young and aged mice models

Identification of age‐specific biomarkers of spinal cord injury: A bioinformatics analysis of young and aged mice models

Biomaterials targeting the microenvironment for spinal cord injury repair: progression and perspectives

Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics

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