Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RGS4 Maintains Chronic Pain Symptoms in Rodent Models

ABSTRACT: There is an imminent need for safe and efficient chronic pain medications. Regulator of G-protein signaling 4 (RGS4) is a multi-functional signal transduction protein, widely expressed in the pain matrix. Here, we demonstrate that RGS4 plays a prominentrole in the maintenance of chronic pain symptoms in male and female mice. Using genetically modified mice, we show a dynamicrole of RGS4 in recovery from symptoms of sensory hypersensitivity deriving from hindpaw inflammation or hindlimb nerveinjury. We also demonstrate an important role of RGS4 actions in gene expression patterns induced by chronic pain states in themouse thalamus. Our findings provide novel insight into mechanisms associated with the maintenance of chronic pain states anddemonstrate that interventions in RGS4 activity promote recovery from sensory hypersensitivity symptoms.

ORGANISM(S): Mus musculus

PROVIDER: GSE138024 | GEO | 2019/09/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RGS4 Maintains Chronic Pain Symptoms in Rodent Models

Project description:RGS4 Maintains Chronic Pain Symptoms in Rodent Models

| PRJNA574183 | ENA

Mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling (RNA-Seq)

Project description:Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia. Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality.

2018-01-19 | GSE102721 | GEO

Mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling [microarray]

Project description:Chronic neuropathic pain is a major morbidity of neural injury, yet its mechanisms are incompletely understood. Hypersensitivity to previously non-noxious stimuli (allodynia) is a common symptom. Here, we demonstrate that the onset of cold hypersensitivity precedes tactile allodynia and this temporal divergence was associated with major differences in global gene expression in dorsal root ganglia (DRG). Transcripts whose expression correlate with the onset of cold allodynia were nociceptor-related, whereas those correlating with tactile hypersensitivity were enriched for immune cell activity. Selective ablation of TrpV1 lineage nociceptors resulted in mice that did not acquire cold allodynia but developed normal tactile hypersensitivity. Whereas, depletion of macrophages or T cells reduced neuropathic tactile allodynia but not cold hypersensitivity. We conclude that neuropathic pain is contributed to by reactive processes of sensory neurons and immune cells, each leading to distinct forms of pain hypersensitivity, potentially allowing effective drug development targeted to each pain modality.

2018-01-19 | GSE89224 | GEO

Ventral hippocampal CA1 modulates pain behaviors in mice with peripheral inflammation

Project description:Chronic pain is one of the most significant and costly medical problems throughout the world. Recent evidence has confirmed the hippocampus as an active modulator of pain chronicity but the underlying mechanisms remain poorly defined. By means of in vivo electrophysiology together with chemogenetic and optogenetic manipulations in freely behaving mice, we identified a neural ensemble in the ventral hippocampal CA1 (vCA1) that showed inhibitory responses to noxious external stimuli, but not to innocuous stimuli. Following peripheral inflammation, this neuronal ensemble became responsive to innocuous stimuli and causally contributed to sensory hypersensitivity in inflammatory animals. Mimicking this inhibition of vCA1 neurons using chemogenetics in naïve mice induced chronic pain-like behavioral changes, whereas activating these vCA1 neurons in mice with chronic peripheral inflammation resulted in a striking reduction of pain-related behaviors. Pathway-specific manipulation of vCA1 projections to the basolateral amygdala (BLA) and infralimbic cortex (IL) showed that these pathways were differentially involved in pain modulation at different temporal stages of chronic inflammatory pain. These results confirm a crucial role of the ventral hippocampus and its circuits in modulating the development of chronic pain in mice.

2022-12-19 | PXD038416 | Pride

Urinary Volatile Compound, Associated with Chronic Inflammation In Interstitial Cystitis

Project description:Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a clinical condition that manifests as a sensory hypersensitivity of unknown cause and is characterized by urinary frequency, bladder discomfort, and pelvic pain. In the present volatolomic study, we have analyzed the VOCs unique to urine specimens obtained from interstitial cystitis patients, in compassion to healthy controls.This is the novel finding from comprehensive and unbiased metabolomics analysis that urinary menthol is decreased in urine specimens from IC patients, and that the reduced menthol level in IC is potentially linked to the chronic inflammation, which is often observed in IC patients

2017-05-09 | ST000603 | MetabolomicsWorkbench

Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain [SmartSeq2]

Project description:Distinct types of dorsal root ganglion sensory neurons may have unique contributions to chronic pain. Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain. However, molecular insights into the primate sensory neurons are missing. Here we classify non-human primate dorsal root ganglion sensory neurons based on their transcriptome and map human pain heritability to neuronal types. First, we identified cell correlates between two major datasets for mouse sensory neuron types. Machine learning exposes an overall cross-species conservation of somatosensory neurons between primate and mouse, although with differences at individual gene level, highlighting the importance of primate data for clinical translation. We map genomic loci associated with chronic pain in human onto primate sensory neuron types to identify the cellular origin of chronic pain. Genome-wide associations for chronic pain converge on two different neuronal types distributed between pain disorders that display different genetic susceptibilities, suggesting both unique and shared mechanisms between different pain conditions.

2021-01-27 | GSE165553 | GEO

Single cell transcriptomics of primate sensory neurons identifies cell types associated with chronic pain [Wafergen]

2021-01-27 | GSE165566 | GEO

Nociceptor HDAC4 regulates inflammatory pain

Project description:Transcriptional alterations are characteristic of persistent pain states but the key regulators remain elusive. Using a conditional knockout (cKO) strategy in mice we sought to determine whether loss of the transcriptional co-repressor histone deacetylase four (HDAC4) would have implications for sensory neuron transcription and nociception. HDAC4 was found to be largely dispensable for transcriptional regulation of naïve sensory neurons but was required for transcriptional responses after injury, with Calca and Trpv1 expression consistently downregulated in HDAC4 cKO compared to littermate controls (0.2-0.44 fold). This downregulation corresponded to reduced sensitivity to capsaicin in vitro (76% +/- 4.4% wildtype capsaicin responders vs 56.9% +/- 4.7% cKO responders) and to reduced thermal hypersensitivity in the complete Freund’s adjuvant model of inflammatory pain (1.3-1.4 fold improvement). These data indicate that HDAC4 is a novel inflammatory pain mediator and may be a good therapeutic target, capable of orchestrating the regulation of multiple downstream effectors. Total RNA was extracted from HDAC4 cKO and HDAC4 fl/fl naïve adult lumbar dorsal root ganglia (n=3/group). mRNA expression was compared using Affymetrix Mouse Gene Arrays (Mouse Gene 2.0ST) run on a GeneChip Fluidics Station 450. Chips were scanned on an Affymetrix GeneChip Scanner.

2015-04-23 | E-GEOD-62405 | biostudies-arrayexpress

Translation Regulation of the Prolactin Receptor Defines Sexually Dimorphic Pain Responses to Prolactin

Project description:Transcriptional control by gonadal hormone nuclear receptors is the foundation for sex-dependent physiological processes, including pain. Our current findings point to sex-dependent translation control as a new mechanism for sexual dimorphisms in pain. We show that hindpaw or spinal administration of exogenous prolactin (PRL) induces thermal and mechanical hyperalgesia in a female-selective fashion. Unexpectedly, PCR and transcriptomic analysis of hindpaw and dorsal root ganglion (DRG) tissues reveal no differences in PRL receptor (Prlr) mRNA between sexes. Variance in overall hindpaw and DRG transcriptomes between females and males were minor. We find that Prlr mRNA and protein is mainly expressed by peptidergic nociceptors as shown by profiling using Prlr reporter mice and electrophysiology, but there are far more peptidergic neurons with functional Prlr in females than in males. In line with this, exogenous PRL increased excitability only in female neurons. Moreover, in male DRG neurons, 6-24 hr estrogen exposure establishes PRL sensitivity in Prlr mRNA+ male neurons that do not show PRL responses under other conditions. PRL-induced behavioral hypersensitivity as well as sensitivity to PRL in female DRG neurons can be ablated by treatment with cap-dependent translation inhibitor 4EGI-1. Spinal cord immunohistochemistry of Prlr reporter mice highlight that Prlr protein is only found in female DRG neurons, but Prlr mRNA localizes to central terminals of male and female sensory neurons. Based on these findings, we propose a novel mechanism for sex-dependent regulation Prlr mRNA translation that renders female DRG neurons uniquely responsive to PRL.

2019-03-01 | GSE121645 | GEO

Translation Regulation of the Prolactin Receptor Defines Sexually Dimorphic Pain Responses to Prolactin

2023-11-17 | GSE161826 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data