Sustained neuronal stimulation activates paraventricular thalamus astrocytes for maintenance of chronic neuropathic pain in mice
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ABSTRACT:
PROVIDER: PRJNA1262926 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33560918_1.fastq.gz | Fastqsanger.gz | |||
| SRR33560918_2.fastq.gz | Fastqsanger.gz | |||
| SRR33560919_1.fastq.gz | Fastqsanger.gz | |||
| SRR33560919_2.fastq.gz | Fastqsanger.gz | |||
| SRR33560920_1.fastq.gz | Fastqsanger.gz |
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Project description:Ongoing nociceptive inputs from peripheral tissues and nerve injuries lead to maladaptive alterations in central nervous system, which drive the transition from acute to chronic pain. Although astrocytes act as dynamic and active players in neuropathic pain states, the contribution of astrocytes in upper brain nucleus in this process remains unclear. Here, we revealed that prolonged neuronal inputs induced by periphery injury leads to astrocyte reactive and downregulation of inward rectifying potassium channel protein 4.1 (Kir4.1) in paraventricular thalamus（PVT）. In turn, reactive PVT astrocytes could maintain the hyperexcitability of neurons, and enhanced projections from PVT to medial prefrontal cortex (mPFC) in the chronicity of neuropathic pain. Notably, we identify a neuro-glial interaction mediating pain chronification in PVT, and clarified Kir4.1 channels as a potential therapeutic target for neuropathic pain treatment.
2025-05-20 | GSE297165 | 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:Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period. We used microarrays to detail the global programme of gene expression underlying the differences in nerve injury between along the postnatal development and identified distinct classes of regulated genes during the injury Experiment Overall Design: We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia, 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour.
2010-01-30 | E-GEOD-15041 | biostudies-arrayexpress
Project description:This program addresses the gene signature associated with DRG in the Chung rat model for neuropathic pain. The Chung neuropathic pain profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in DRG of the Sprague Dawley rats following spinal nerve ligation compared to the sham-operated controls.
2013-03-22 | E-GEOD-38038 | biostudies-arrayexpress
Project description:Treating neuropathic pain is challenging and novel non-opioid based medicines are needed. Using unbiased receptomics, transcriptomic analyses, immunofluorescence and in situ hybridization, expression of the orphan GPCR (oGPCR) GPR160 increased in the rodent dorsal horn of the spinal cord (DH-SC) following traumatic nerve injury. Genetic and immunopharmacological approaches demonstrated that GPR160 inhibition in the spinal cord prevented and reversed neuropathic pain in male and female rodents without altering normal pain response. GPR160 inhibition in the spinal cord attenuated sensory processing in the thalamus, a key relay in the sensory discriminative pathways of pain. We also identified cocaine- and amphetamine-regulated transcript peptide (CARTp) as a GPR160 ligand. Inhibiting endogenous CARTp signaling in spinal cord attenuated neuropathic pain, whereas exogenous intrathecal (i.th.) CARTp evoked painful hypersensitivity through GPR160-dependent ERK and cAMP response element-binding protein (CREB). Our findings de-orphanize GPR160, identify it as a determinant of neuropathic pain and potential therapeutic target, and provide insights to its signaling pathways. CARTp is involved in many diseases including depression, reward and addiction, de-orphanization of GPR160 is a major step forward understanding the role of CARTp signaling in health and disease.
2020-02-20 | GSE143895 | GEO
Project description:• Project description: Why only half of the idiopathic peripheral polyneuropathy (IPN) patients develop neuropathic pain is unknown. By conducting a proteomics analysis on IPN patients, we aimed to discover proteins and new pathways that are associated with neuropathic pain. We conducted unbiased mass-spectrometry proteomics analysis on blood plasma from 31 IPN patients with severe neuropathic pain and 29 IPN patients with no pain, to investigate protein biomarkers and protein-protein interactions associated with neuropathic pain. Univariate modeling was done with Linear mixed modeling (LMM) and corrected for multiple testing. Multivariate modelling was performed using elastic net analysis and validated with internal cross validation and bootstrapping.
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Project description:Pain sensing neurons, nociceptors, are key drivers of neuropathic pain. We used translating ribosome affinity purification (trap) to comprehensively characterize up- and down-regulated mRNA translation in Scn10a-positive nociceptors in chemotherapy-induced neuropathic pain. We provide evidence that an underlying mechanism driving these changes in gene expression is a sustained mTORC1 activation driven by MNK1-eIF4E signaling. RagA, a GTPase controlling mTORC1 activity, is identified as a novel target of MNK1-eIF4E signaling, demonstrating a new link between these distinct signaling pathways. Neuropathic pain and RagA translation are strongly attenuated by genetic ablation of eIF4E phosphorylation, MNK1 elimination or treatment with the MNK inhibitor eFT508. We reveal a novel translational circuit for the genesis of neuropathic pain with important implications for next generation neuropathic pain therapeutics.
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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.
2014-09-29 | GSE60033 | GEO
Project description:Neuropathic pain (NP) is a complex chronic pain due to the nervous system damage or diseases.During NP development and progression, the neuroinflammation has been observed along the pain pathways from the spinal cord to the thalamus and the parietal cortex. It may be caused by the activation of glial cells, especially microglia, with production of cytokines and other inflammatory mediators within the central nervous system (CNS), especially in spinal cord. In this study, we used high-throughput RNA-seq technology to detect the global gene expression in spinal cord of rats in sham group and CCI model group(an animal model of neuropathic pain), and the differentially expressed genes between diseases and control group were obtained.Significant differentially expressed genes (DEGs) of the Sham vs. CCI groups were identified using the criteria of a fold change>1.5 and P value <0.05. Finally, we focused on C/EBPβ-Clec7a Cross-talk-mediated NLRP3 Inflammasome-dependent Pyroptosis pathway and further studied its role in neuropathic pain.
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Project description:Neuropathic pain (NP) is a complex chronic pain due to the nervous system damage or diseases.During NP development and progression, the neuroinflammation has been observed along the pain pathways from the spinal cord to the thalamus and the parietal cortex. It may be caused by the activation of glial cells, especially microglia, with production of cytokines and other inflammatory mediators within the central nervous system (CNS), especially in spinal cord. In this study, we used microarrays to detect the global gene expression in spinal cord of rats in sham group and CCI model group(an animal model of neuropathic pain), and the differentially expressed genes between diseases and control group were obtained.
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