The Nociceptive Activity of Peripheral Sensory Neurons is Modulated by the Neuronal Membrane Proteasome
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE261727 | GEO | 2024/04/12
REPOSITORIES: GEO
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Project description:Nerve injury induces long-lasting pathological pain, namely neuropathic pain (NP), which is dysfunction of the whole pain transmission process, including dorsal root ganglia (DRG) in peripheral nerve system (PNS). Melatonin is well known over a long period of time as hormone of circadian rhythm closely related with the various aspects of pain conditions. Melatonin and melatonin related receptors (MTR1A and MTR1B) exerted amazing analgesic effect in many acute and chronic pain experimental studies, including electrically induced pain, thermally induced pain, mechanical induction of pain and chemical induction of pain. However, the anti-nociceptive action of melatonin in NP is still controversial and unclear. In the present study, our research firstly demonstrated the expression of melatonin receptors in the DRGs, and what more interesting is that MTR1A and MTR1B have a completely different cell type location (MTR1A in the satellite cells and MTR1B in the neurons). In order to get a basic glance at the effects of melatonin and MTR1B on the DRG neurons, a microarray analysis is applied to screen the pain related different expression genes in the primary DRGs cultured neurons with treatment of 1mM melatonin, 100μM MTR1B agonist 8-M-PDOT or vehicle (1% ethanol of normal saline). Subsequent examination was performed, and the finding suggested that melatonin suppressed neuropathic pain via MTR1B dependent and independent pathways in dorsal root ganglia neurons. And MTR1B in DRG may be a potential therapeutic target for NP.
2016-11-05 | GSE89289 | GEO
Project description:Maladaptive changes of nerve injury–associated genes in dorsal root ganglia (DRGs) are critical for neuropathic pain genesis. Emerging evidence supports the role of long noncoding RNAs (lncRNAs) in regulating gene transcription. Here we identified a conserved lncRNA, named nerve injury–specific lncRNA (NIS-lncRNA) for its upregulation in injured DRGs exclusively in response to nerve injury. This upregulation was triggered by nerve injury–induced increase in DRG ELF1, a transcription factor that bound to the NIS-lncRNA promoter. Blocking this upregulation attenuated nerve injury–induced CCL2 increase in injured DRGs and nociceptive hypersensitivity during the development and maintenance periods of neuropathic pain. Mimicking NIS-lncRNA upregulation elevated CCL2 expression, increased CCL2-mediated excitability in DRG neurons, and produced neuropathic pain symptoms. Mechanistically, NIS-lncRNA recruited more binding of the RNA-interacting protein FUS to the Ccl2 promoter and augmented Ccl2 transcription in injured DRGs. Thus, NIS-lncRNA participates in neuropathic pain likely by promoting FUS-triggered DRG Ccl2 expression and may be a potential target in neuropathic pain management.
2022-06-15 | GSE206043 | GEO
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:The mammalian embryos Caudal Lateral Epiblast (CLE) harbours bipotent progenitors, called Neural Mesodermal Progenitors (NMPs), that contribute to the spinal cord and the paraxial mesoderm throughout axial elongation. Here we performed a single cell analysis of different in vitro NMPs populations produced either from embryonic stem cells (ESCs) or epiblast stem cells (EpiSCs) and compared them to E8.25 CLE mouse embryos. In our analysis of this region our findings challenge the notion that NMPs can be defined by the exclusive coexpression of Sox2 and T at mRNA level. We analyse the in vitro NMP-like populations using a purpose-built Support Vector Machine (SVM) based on the embryo CLE and use it as a classification model to compare the in vivo and in vitro populations. Our results show that NMP differentiation from ESCs, leads to heterogeneous progenitor populations with few NMP-like cells, as defined by the SVM algorithm, whereas starting with EpiSCs, yields a high proportion of cells with the embryo NMP signature. We find that the population from which the Epi-NMPs are derived in culture contains a node-like population, which leads to suggest that this population probably maintains the expression of T in vitro and thereby a source of NMPs. In conclusion, differentiation of EpiSCs into NMPs reproduces events in vivo and suggests a sequence of events for the emergence of the NMPs population.
2019-06-11 | GSE132504 | GEO
Project description:Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained postoperative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatics analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the 7 miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve injuries. To identify the miRs that were differentially dysregulated between Tibial-SNI and Sural-SNI, we first performed 12 microarrays in a limited number of samples (in four individual DRGs per group: Sham, Tibial-SNI and Sural-SNI; two L3-DRG and two L4-DRG). Then, miRs identified as having differential expression were corroborated with real time qRT-PCR in RNA isolated from individual DRGs (L3, L4 and L5) derived from 4 rats per group (not presented here, but in the manuscript).
2014-09-29 | E-GEOD-60033 | biostudies-arrayexpress
Project description:Undifferentiated human embryonic stem cells (hESCs) were treated with WNT and FGF agonists for three days to generate NMP-like axial progenitors (NMPs).
2021-09-23 | GSE184622 | GEO
Project description:<p>RNA sequencing was performed on human DRGs and relative gene abundances were calculated.</p> <p>Various analyses were performed:</p> <p> <ol> <li>Human DRG gene expression profiles were contrasted with a panel of gene expression profiles of relevant tissues in human and mouse ( integrating, among other sources, datasets from ENCODE and GTex ) in order to identify.</li> <ol type="a"> <li>DRG-enriched gene expression, co-expression modules of DRG-expressed genes, and key transcriptional regulators in humans.</li> <li>Contrasting the human and mouse DRG transcriptomes to identify DRG-enriched gene expression patterns that were conserved between human and mouse, identifying putative cell types of expression of these genes, and potential known drugs that might target the corresponding gene products.</li> <li>Characterization of non-coding RNA profile of human and mouse DRGs.</li> <li>Characterization of DRG-enriched alternative splicing and alternative transcription start site usage based transcript variants in humans and mouse, and the overlap between these two species.</li> <li>Contrasting of human DRG and GTex human tibial nerve samples to identify putative axonally transported mRNAs in sensory neurons.</li> </ol> <li>Human DRG transcriptomes from donors suffering from neuropathic and/or chronic pain were contrasted with controls to identify.</li> <ol type="a"> <li>Differentially expressed genes, pathways and regulators path play a potential role in neuronal plasticity, electrophysiological activity, immune signaling and response.</li> <li>Predictive models (Random Forests) were built to jointly predict the sex and pain state of samples based on information contained solely in autosomal gene expression profile.</li> <li>Gene co-expression modules were identified and gene set enrichment analysis performed.to identify sample - pathway associations, and to broadly characterize plasticity in human DRG cell types.</li> </ol> </ol> </p>
| phs001158 | dbGaP
Project description:Purpose: The goalsof this study was to compare the transcriptome profiling of dorsal root ganglia (DRG) of animals injected intrathecally with IL4-10 FP, the combination of IL4+IL10 or vehicle, one week after induction of persistent inflammatory pain. Methods: Mice received an intraplantar injection of carrageenan and one week developing inflammatory pain were intrathecally injected with IL4-10 FP, IL4+IL10 or PBS. DRGs were isolated and RNA libraries were prepared with the poly A selection method followed by multiplexing and sequencing on the Illumina NextSeq500® platform in a 1 × 75bp single-read and 350 million reads per lane (Utrecht Sequencing Facility) Results: In vivo IL4-10 FP induces a differential transcriptome than the combination of cytokines in mice with persistent inflammatory pain. Conclusions: The superior analgesic effect observed in mice treated with IL4-10 FP compared to mice injected with the naïve cytokines is derived from an induction of a different transcriptome on the lumbar DRGs.
2021-02-28 | GSE150795 | GEO
Project description:We have established functions of the stimulus dependent MAPKs, ERK1/2 and ERK5 in DRG, motor neuron, and Schwann cell development. Surprisingly, many aspects of early DRG and motor neuron development were found to be ERK1/2 independent and Erk5 deletion had no obvious effect on embryonic PNS. In contrast, Erk1/2 deletion in developing neural crest resulted in peripheral nerves that were devoid of Schwann cell progenitors, and deletion of Erk1/2 in Schwann cell precursors caused disrupted differentiation and marked hypomyelination of axons. The Schwann cell phenotypes are similar to those reported in neuregulin-1 and ErbB mutant mice and neuregulin effects could not be elicited in glial precursors lacking Erk1/2. ERK/MAPK regulation of myelination was specific to Schwann cells, as deletion in oligodendrocyte precursors did not impair myelin formation, but reduced precursor proliferation. Our data suggest a tight linkage between developmental functions of ERK/MAPK signaling and biological actions of specific RTK-activating factors. Microarray analysis on RNA extracts derived from E12.5 Erk1/2CKO(Wnt1) and wildtype DRGs
2010-10-16 | E-GEOD-24730 | biostudies-arrayexpress
Project description:Two out-bred rat selection lines were separated to produce different hypersensitivity phenotypes following nerve injury. These lines were termed High Pain and Low Pain (HP or LP). Each sub-strain was either subject to a Sham surgery or a Spinal Nerve Ligation (SNL) surgery to the L4 and L5 spinal nerves. Three days following surgery L4/L5 Dorsal Root Ganglia (DRG) were dissected from these animals. For the rat line separation protocol see: Devor M, Raber P (1990) Heritability of symptoms in an experimental model of neuropathic pain. Pain 42:51-67. 12 Hybridizations, 3 per condition; Sham HP DRG; 3 day SNL HP DRG; Sham LP DRG; 3 day SNL LP DRG.
2015-02-19 | E-GEOD-63442 | biostudies-arrayexpress