A Transcriptomic Analysis of Neuropathic Pain in the Spinal Cord after Nerve Injury
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE175760 | GEO | 2022/04/05
REPOSITORIES: GEO
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Project description:To further reveal the mechanism of neuropathic pain, we simulated neuropathic pain by constructing a chronic constriction injury of the sciatic nerve (CCI) model, followed by quantitative proteomic analysis of rat spinal cord cell nuclei at 1 day, 7 days and sham-operated groups after CCI. A total of 3 samples from each group were used. A total of 5039 proteins were identified in this study, of which 4469 proteins contained quantitative information. Differential proteins were defined by a threshold of change >1.3-fold and t-test p-value <0.05.v
2023-01-17 | PXD034960 | Pride
Project description:Neuropathic pain is a troublesome pathological condition without suitable treatments. In this study, we performed RNA sequencing (RNA-seq) analysis to reveal transcriptomic profiles of Anterior Cingulate Cortex (ACC) from chronic constriction injury (CCI) rats. We found 1628 differentially expressed genes (DEGs) were mainly involved in the inflammatory and immune process. Besides, cytokine signaling and other cell-defense related pathways mainly contribute to the occurrence and development of neuropathic pain. Then we classified the DEGs based on the time trend. Our results suggested that chemokines played a vital role in pain, and moreover, CCL5, CXCL9 and CXCL13, compared with CCL2, CCL3, CCL4, CCL6 and CCL7 had different time-dependent manners. In a word, targeting chemokines is of great significance to explore specific mechanisms and develop suitable drugs for neuropathic pain.
2022-04-05 | GSE172133 | GEO
Project description:Neuropathic pain is a prevalent and debilitating chronic disease that is characterized by activation in glial cells in various pain-related regions within the central nervous system. Recent studies have suggested a sexually dimorphic role of microglia in the maintenance of neuropathic pain in rodents. Here, we utilized RNA sequencing analysis of microglia to identify whether there is a common neuropathic microglial signature and characterize the sex differences in microglia in pain-related regions in nerve injury and chemotherapy-induced peripheral neuropathy mouse models. Whilst mechanical allodynia and behavioral changes were observed in all models, transcriptomic analysis of microglia revealed no common transcriptional changes in spinal and supraspinal regions and in different neuropathic models. However, there was a substantial change in microglial gene expression within the ipsilateral lumbar spinal cord 7-days after chronic constriction injury (CCI) of the sciatic nerve. Both sexes upregulated genes associated with inflammation, phagosome, and lysosome activation, though males revealed a prominent global transcriptional shift not observed in female mice. This study demonstrates a lack of a common neuropathic microglial signature and indicates distinct sex differences in spinal microglia, suggesting they contribute to the sex-specific pain processing following nerve injury.
2021-07-27 | GSE180627 | GEO
Project description:Previous studies have suggested that astrocyte activation in the spinal dorsal horn may play an important role in the development of chronic neuropathic pain; but the mechanisms involved in astrocyte activation and their modulatory effects remain unknown. The inward rectifying potassium channel protein 4.1 (Kir4.1) is the most important background K+ channel in astrocytes. However, how Kir4.1 is regulated and contributes to behavioral hyperalgesia in chronic pain is unknown. In this study, single-cell RNA sequencing analysis indicated that the expression of Kir4.1 and Methyl-CpG-binding protein 2 (MeCP2) were both decreased in spinal astrocytes after chronic constriction injury (CCI) in a mouse model. Conditional knockout of the Kir4.1 channel in spinal astrocytes led to hyperalgesia; and overexpression of the Kir4.1 channel in spinal cord relieved CCI-induced hyperalgesia. Expression of spinal Kir4.1 after CCI was regulated by MeCP2. Electrophysiological recording in spinal slices showed that knockdown of Kir4.1 significantly regulated the excitability of astrocytes and then functionally changed the firing patterns of neurons in dorsal spinal cord. Therefore, targeting spinal Kir4.1 maybe an underlying treatment for hyperalgesia in chronic neuropathic pain.
2022-07-24 | GSE208766 | GEO
Project description:To investigate the role of DNA methylation in modulating chronic neuropathic pain (NPP), and identify possible target genes of DNA methylation involved in this process. The chronic constriction injury (CCI) induced NPP model was used. The Arraystar Rat RefSeq Promoter Arrays were used to identify the methylation profiles at the genome-wide level in the DNA promoter regions of the lumbar spinal cord in rats 14 Days following CCI surgery. The underlying genes with differential methylation were then identified and submitted to Gene Ontology and pathway analysis. Methyl-DNA immunoprecipitation quantitative PCR (MeDIP-qPCR) and quantitative reverse transcription-PCR (RT‒qPCR) were used to confirm gene methylation and expression.
2022-12-07 | GSE219038 | GEO
Project description:To search for novel m6A-modified transcripts that are involved in the genesis of neuropathic pain, We collected the ipsilateral spinal cord at 7 days after chronic constriction injury and performed m6A peak profiling using MeRIP-seq
2021-03-29 | GSE171004 | GEO
Project description:Objective: Chronic pain is a major problem in patients with spinal cord injury (SCI). According to different studies, approximately 70% of patients with SCI experience persistent pain. Although previous gene expression profiling studies have been conducted in animal models, gene expression profiling study in human whole blood has not been reported yet. The objective of this study was to define the gene expression profile of neuropathic pain in spinal cord injured patients. Materials and Methods: We performed gene expression analysis including 20.000 genes using Affymetrix GeneChip® Primeview™ Human Gene Expression Arrays. For confirmation of expression levels of selected genes, we performed real time polymerase chain reaction. We gathered samples from periferic blood mononuclear cells. Data of twelve patients with intractable neuropathic pain was compared with thirteen patients who don’t have pain. All patients have complete injuries with a level of injury above T5. Results: A total of 16 differentially expressed genes including 9 up-regulated and 7 down-regulated were obtained with a cut-off degree at 4 fold change. EIF1AY, RPS4Y1, DDX3Y, RPL31, ETS1, KLF3, JUN, CYorf15B, and ERAP2 were in up-regulated and HLA-C, XIST, C4BPA, FAM118A, ZNF506, OVOS2, and C1D were in down-regulated group. KEGG pathway database showed that 14.6% of genes were enriched in the nodes of immune system. Real time polymerase chain reaction analyses did not increase to statistically significant levels for confirmation of gene expression analyze results. Conclusions: Considering these data, findings of this first gene expression study in humans with SCI might provide valuable information for future targets for understanding neuropathic pain pathogenesis. The results of gene expression analyses were not confirmed by real time polymerase chain reaction. Studies with larger sample size are needed for confirmation. This is a cross-sectional study with a control group. Patients were divided into two groups according to intractable neuropathic pain existence.There were 12 patients in group A (Patients with pain) and 13 patients in control group.
2015-06-16 | E-GEOD-69901 | biostudies-arrayexpress
Project description:Expression profiling of L4 and L5 Dorsal Root Ganglion (DRG) in the spinal nerve ligation model of neuropathic pain. The goal of the study was to identify genes involved in neuropathic pain
2011-10-18 | GSE24982 | GEO
Project description:Functionally distinct subtypes/clusters of dorsal root ganglion (DRG) neurons may play different roles in nerve regeneration and pain. However, details about their transcriptomic changes under neuropathic pain conditions remain unclear. Chronic constriction injury (CCI) of the sciatic nerve represents a well-established model of neuropathic pain, and we conducted single-cell RNA-sequencing (scRNA-seq) to characterize subtype-specific perturbations of transcriptomes in lumbar DRG neurons on day 7 post-CCI. By using PirtEGFPf mice that selectively express an enhanced green fluorescent protein in DRG neurons, we established a highly efficient purification process to enrich neurons for scRNA-seq. We observed the emergence of four prominent CCI-induced clusters and a loss of marker genes in injured neurons. Importantly, a portion of injured neurons from several clusters were spared from injury-induced identity loss, suggesting subtype-specific transcriptomic changes in injured neurons. Moreover, uninjured neurons, which are necessary for mediating the evoked pain, also demonstrated cell-type-specific transcriptomic perturbations in these clusters, but not in others. Notably, male and female mice showed differential transcriptomic changes in multiple neuronal clusters after CCI, suggesting transcriptomic sexual dimorphism in DRG neurons after nerve injury. Using Fgf3 as a proof-of-principle, RNAscope study provided further evidence of increased Fgf3 in injured neurons after CCI, supporting scRNA-seq analysis, and calcium imaging study unraveled a functional role of Fgf3 in neuronal excitability. These findings may contribute to the identification of new target genes and the development of DRG neuron cell-type-specific therapies for optimizing neuropathic pain treatment and nerve regeneration.
2022-10-24 | GSE216039 | GEO
Project description:We produced single-cell transcriptomes from the mouse spinal cord using Drop-seq in animals modeling neuropathic pain and superficial injury (SI) controls. We used the spared nerve injury (SNI) model of neuropathic pain. ~10,000 cells from sham surgery controls and ~9,000 cells from SNI animals were sequenced. Unbiased cell clustering yielded 66 spinal cell subtypes sequenced at relatively low depth (~1200 transcripts/cell). Comparisons between SI and SNI cells were performed to investigate cell-specific differences during a neuropathic pain state.
2021-03-04 | GSE134003 | GEO