Effect of human genetic variability on gene transcription in dorsal root ganglia and association with pain phenotypes [exon-level]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE78148 | GEO | 2017/05/10
SECONDARY ACCESSION(S): PRJNA312784
REPOSITORIES: GEO
Similar Datasets
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
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.
2023-01-09 | MSV000091027 | MassIVE
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.
2023-08-27 | GSE235230 | GEO
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.
2023-01-09 | MSV000091027 | GNPS
Project description:Acute pain serves as a protective mechanism, guiding the organism away from actual or potential tissue injury. In contrast, chronic pain is a debilitating condition without any obvious physiological function. The transition to, and the maintenance of chronic pain require new gene expression to support biochemical and structural changes within the pain pathway. The regulation of gene expression at the level of mRNA translation has emerged as an important step in the control of protein expression in the cell. Recent studies show that signaling pathways upstream of mRNA translation, such as mTORC1 and ERK, are upregulated in chronic pain conditions, and their inhibition effectively alleviates pain in several animal models. Despite this progress, mRNAs whose translation is altered in chronic pain conditions remain largely unknown. Here, we performed genome-wide translational profiling of dorsal root ganglion (DRG) and spinal cord dorsal horn tissues in a mouse model of neuropathic pain, spared nerve injury (SNI), using the ribosome profiling technique. We identified distinct subsets of mRNAs that are differentially translated in response to nerve injury in both tissues. We discovered key converging upstream regulators and pathways linked to mRNA translational control and neuropathic pain. Our data are crucial for the understanding of mechanisms by which mRNA translation promotes persistent hypersensitivity after nerve injury.
2018-12-18 | GSE123919 | GEO
Project description:Inflammation plays a role in neuropathic pain conditions as well as in pain induced solely by an inflammatory stimulus. Robust mechanical hyperalgesia and allodynia can be induced by locally inflaming the L5 dorsal root ganglion (DRG) in rat. This model allows investigation of the contribution of inflammation per se to chronic pain conditions. Most previous microarray studies of DRG gene expression have investigated neuropathic pain models involving axon transection. To examine the role of inflammation, we used microarray methods to examine gene expression 3 days after local inflammation of the L5 DRG in rat. We observed significant regulation in a large number of genes (23% of observed transcripts), and examined 221 (3%) with a fold-change of 1.5-fold or more in more detail. Immune-related genes were the largest category in this group and included members of the complement system as well as several pro-inflammatory cytokines. However, these upregulated cytokines had no prior links to peripheral pain in the literature other than through microarray studies, though most had previously described roles in CNS (especially neuroinflammatory conditions) as well as in immune responses. The L5 dorsal root ganglion (DRG) was locally inflamed with zymosan/Incomplete Freund's Adjuvant. DRG were isolated 3 days later. Each sample was RNA extracted from a single DRG. 6 samples from rats with local DRG inflammation were compared with 6 samples from sham-operated rats.
2012-06-21 | E-GEOD-38859 | biostudies-arrayexpress
Project description:Chronic, often intractable pain is caused by neuropathic conditions such as peripheral nerve injury (PNI) and spinal cord injury (SCI). These conditions are associated with alterations in gene and protein expression correlated with functional changes in somatosensory neurons having cell bodies in dorsal root ganglia (DRGs). Most studies of DRG transcriptional alterations have utilized PNI models where axotomy-induced changes important for regeneration may overshadow changes that drive neuropathic pain. Both PNI and SCI produce DRG neuron hyperexcitability linked to pain, but contusive SCI produces little peripheral axotomy or peripheral nerve inflammation. Thus, comparison of transcriptional signatures of DRGs across PNI and SCI models may highlight pain-associated transcriptional alterations that don’t depend on peripheral axotomy and associated effects such as peripheral Wallerian degeneration. Data from our rat thoracic SCI experiments were combined with meta-analysis of whole-DRG RNA-seq datasets from prominent rat PNI models. Striking differences were found between transcriptional responses to PNI and SCI, especially in regeneration-associated genes and long noncoding RNAs. Many transcriptomic changes after SCI were also found after corresponding sham surgery, indicating they were caused by injury to surrounding tissue rather than to the spinal cord itself. Another unexpected finding was of few transcriptomic similarities between any rat neuropathic pain model and the only reported transcriptional analysis of human DRGs linked to neuropathic pain. These findings show that DRGs exhibit complex transcriptional responses to central and peripheral neural and tissue injury. Although few genes in DRG cells show similar changes in gene expression across all these painful conditions, the few widely shared transcriptional alterations promise novel insights into fundamental mechanisms within DRGs that can drive neuropathic pain.
2022-10-20 | GSE202111 | GEO
Project description:Background: Mirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, including complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remained largely unknown. The purpose of this study is to perform an expression profiling to identify genes related with MIP in an animal model of CRPS-I. Methods: We established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining and animal behavioral assays were used to screen potential genes in contralateral dorsal root ganglia (DRG) that may be involved in MIP. Results: The CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs. control rats. The expression changes of several representative DEGs were verified by qPCR. Bioinformatics analysis indicated that immune system process, innate immune response and cell adhesion were among the mostly enriched biological processes, which are all important processes involved in pain sensitization, neuroinflammation and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small- to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and pain mechanism in MIP. Conclusions: We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for investigating MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.
2021-09-15 | GSE174299 | GEO
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
Project description:The study pursued dual goals: To advance mRNA-seq bioinformatics towards unbiased transcriptome capture and to demonstrate its potential for discovery in neuroscience by applying the approach to an in vivo model of neurological disease. We found that 12.4% of known genes were induced and 7% were suppressed in the dysfunctional (but anatomically intact) L4 dorsal root ganglion (DRG) 2 weeks after L5 spinal Nerve Ligation (SNL). A new algorithm for agnostic mapping of pre-mRNA splice junctions (SJ) achieved a precision of 97%. mRNA-seq of L4 DRG 2 weeks and 2 months after L5 spinal nerve ligation. CONTROL and SNL were used to identify differential gene expression between chronic pain and standard conditions in Rattus norvegicus. CONTROL and SNL and PILOT were used to perform 'agnostic splice site discovery' in the nervous system transcriptome in Rattus norvegicus
2010-05-01 | E-GEOD-20895 | biostudies-arrayexpress