Mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling
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ABSTRACT:
PROVIDER: PRJNA399497 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5937650_1.fastq.gz | Fastqsanger.gz | |||
| SRR5937650_2.fastq.gz | Fastqsanger.gz | |||
| SRR5937660_1.fastq.gz | Fastqsanger.gz | |||
| SRR5937660_2.fastq.gz | Fastqsanger.gz | |||
| SRR5937670_1.fastq.gz | Fastqsanger.gz |
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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
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
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-01-18 | GSE102937 | GEO
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 in a model of partial nerve injury, and this temporal divergence was associated with major differences in global gene expression in innervating dorsal root ganglia. Transcripts whose expression change correlates with the onset of cold allodynia were nociceptor related, whereas those correlating with tactile hypersensitivity were immune cell centric. 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 incorporates reactive processes of sensory neurons and immune cells, each leading to distinct forms of hypersensitivity, potentially allowing drug development targeted to each pain type.
| S-EPMC5908229 | biostudies-literature
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:Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein synthesis; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found mTOR activation in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. Combining transcriptomic profiling, electrophysiological recording and pharmacologic manipulations, we demonstrated that activated mTOR promoted neuropeptide Y (NPY) induction in mechanoreceptors and that NPY acted on Y2 receptors (Y2R) but not Y1R to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented its function. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.
2022-09-01 | GSE184014 | GEO
Project description:Mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling [microarray]
| PRJNA350723 | ENA
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:Mechanistic differences in neuropathic pain modalities revealed by correlating behavior with global expression profiling (RNA-Seq)
| PRJNA398499 | ENA
Project description:This program addresses the gene signature associated with DRG in the Chung rat model for neuropathic pain.
2013-03-22 | GSE38038 | GEO