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Effect of human genetic variability on gene transcription in dorsal root ganglia and association with pain phenotypes [exon-level]

ABSTRACT: Single nucleotide polymorphisms (SNP) can affect mRNA gene expression, in a tissue-specific manner. In this work we survey association of SNP alleles with mRNA gene expression in human dorsal root ganglions (DRG) to gain insights into pathophysiology of pain phenotypes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE78148 | GEO | 2017/05/10

SECONDARY ACCESSION(S): PRJNA312784

REPOSITORIES: GEO

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Effect of human genetic variability on gene transcription in dorsal root ganglia and association with pain phenotypes [transcript-level]

Project description:Single nucleotide polymorphisms (SNP) can affect mRNA gene expression, in a tissue-specific manner. In this work we survey association of SNP alleles with mRNA gene expression in human dorsal root ganglions (DRG) to gain insights into pathophysiology of pain phenotypes.

2017-05-10 | GSE77968 | GEO

Integrative multiomic analyses of dorsal root ganglia in diabetic neuropathic pain using proteomics, phosphoproteomics, and metabolomics

Project description:Diabetic peripheral neuropathy (DPN) is characterized by spontaneous pain in the extremities. Incidence of DPN continues to rise with the global diabetes epidemic. However, there remains a lack of safe, effective analgesics to control this chronic painful condition. Dorsal root ganglia (DRG) contain soma of sensory neurons and modulate sensory signal transduction into the central nervous system. In this study, we aimed to gain a deeper understanding of changes in molecular pathways in the DRG of DPN patients with chronic pain. We recently reported transcriptomic changes in the DRG with DPN. Here, we expand upon those results with integrated metabolomic, proteomic, and phosphoproteomic analyses to compare the molecular profiles of DRG from DPN donors and DRG from control donors without diabetes or chronic pain. Our analyses identified decreases of select amino acids and phospholipid metabolites in the DRG from DPN donors, which are important for cellular maintenance. Additionally, our analyses revealed changes suggestive of extracellular matrix (ECM) remodeling and altered mRNA processing. These results reveal new insights into changes in the molecular profiles associated with DPN.

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GNPS - Integrative multiomic analyses of dorsal root ganglia in diabetic neuropathic pain using proteomics, phosphoproteomics, and metabolomics

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Defective Branched-Chain Amino Acid Catabolism in Dorsal Root Ganglia Contributes to Mechanical Pain

Project description:Impaired branched-chain amino acid (BCAA) catabolism has recently been implicated in the development of mechanical pain, but the underlying molecular mechanisms are unclear. Here we report that defective BCAA catabolism in dorsal root ganglion (DRG) neurons sensitizes mice to mechanical pain by increasing lactate production and expression of the mechanotransduction channel Piezo2. In high-fat diet-fed obese mice, we observe downregulation of PP2Cm, a key regulator of the BCAA catabolic pathway, in DRG neurons. Mice with conditional knockout of PP2Cm in DRG neurons exhibit mechanical allodynia under normal or SNI-induced neuropathic injury conditions. Furthermore, the VAS scores in the plasma of patients with peripheral neuropathic pain are positively correlated with BCAA contents. Mechanistically, defective BCAA catabolism in DRG neurons promotes lactate production through glycolysis, which increases H3K18la modification and drives Piezo2 expression. Inhibition of lactate production or Piezo2 silencing attenuates the pain phenotype of knockout mice in response to mechanical stimuli. Therefore, our study demonstrates a causal role of defective BCAA catabolism in mechanical pain by enhancing metabolite-mediated epigenetic regulation.

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Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-05-10 | GSE78150 | GEO

Transcription profiling of rat dorsal root ganglia from CCI and Seltzer models of neuropathic pain

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RNA-seq of rat dorsal root ganglia after ligation to investigate central nervous system transcriptomics in chronic pain using agnostic splice site discovery methods

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Effect of Human Genetic Variability on Gene Expression in Dorsal Root Ganglia and Association with Pain Phenotypes.

Project description:Dorsal root ganglia (DRG) relay sensory information to the brain, giving rise to the perception of pain, disorders of which are prevalent and burdensome. Here, we mapped expression quantitative trait loci (eQTLs) in a collection of human DRGs. DRG eQTLs were enriched within untranslated regions of coding genes of low abundance, with some overlapping with other brain regions and blood cell cis-eQTLs. We confirm functionality of identified eQTLs through their significant enrichment within open chromatin and highly deleterious SNPs, particularly at the exon level, suggesting substantial contribution of eQTLs to alternative splicing regulation. We illustrate pain-related genetic association results explained by DRG eQTLs, with the strongest evidence for contribution of the human leukocyte antigen (HLA) locus, confirmed using a mouse inflammatory pain model. Finally, we show that DRG eQTLs are found among hits in numerous genome-wide association studies, suggesting that this dataset will help address pain components of non-pain disorders.

| S-EPMC5524461 | biostudies-literature

Transcription profiling of rat dorsal root ganglia from L5 spinal nerve ligation model of neuropathic pain

Project description:DRG samples were extracted at 28 and 50 days from L5 spinal nerve ligated rats and sham operated rats. Samples were pooled for each time point per group and hybridised to duplicate to RG_u34 genchips (A, B and C chips). Experiment Overall Design: Samples were pooled and therefore no biological replication was possible on the arrays

2007-11-06 | E-GEOD-2884 | biostudies-arrayexpress

A Transcriptomic Analysis of Neuropathic Pain in Rat Dorsal Root Ganglia Following Peripheral Nerve Injury

Project description:In this study, we screened the differentially expressed genes (DEGs) in the dorsal root ganglia (DRG) from rats with sham or partial sciatic nerve ligation (pSNL) surgery 7 days using RNAseq technique to explore the molecular mechanisms of neuropathic pain

2020-06-30 | GSE117526 | GEO

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