Dataset Information

Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord.

ABSTRACT: To obtain a thorough understanding of chronic pain, large-scale molecular mapping of the pain axis at the protein level is necessary, but has not yet been achieved. We applied quantitative proteome profiling to build a comprehensive protein compendium of three regions of the pain neuraxis in mice: the sciatic nerve (SN), the dorsal root ganglia (DRG), and the spinal cord (SC). Furthermore, extensive bioinformatics analysis enabled us to reveal unique protein subsets which are specifically enriched in the peripheral nervous system (PNS) and SC. The immense value of these datasets for the scientific community is highlighted by validation experiments, where we monitored protein network dynamics during neuropathic pain. Here, we resolved profound region-specific differences and distinct changes of PNS-enriched proteins under pathological conditions. Overall, we provide a unique and validated systems biology proteome resource (summarized in our online database painproteome.em.mpg.de), which facilitates mechanistic insights into somatosensory biology and chronic pain-a prerequisite for the identification of novel therapeutic targets.

SUBMITTER: Barry AM

PROVIDER: S-EPMC6103001 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord.

Barry Allison M AM Sondermann Julia R JR Sondermann Jan-Hendrik JH Gomez-Varela David D Schmidt Manuela M

Frontiers in molecular neuroscience 20180814

To obtain a thorough understanding of chronic pain, large-scale molecular mapping of the pain axis at the protein level is necessary, but has not yet been achieved. We applied quantitative proteome profiling to build a comprehensive protein compendium of three regions of the pain neuraxis in mice: the sciatic nerve (SN), the dorsal root ganglia (DRG), and the spinal cord (SC). Furthermore, extensive bioinformatics analysis enabled us to reveal unique protein subsets which are specifically enrich ...[more]

PMID: 30154697

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Project description:Objective: Chronic pain is a major problem in patients with spinal cord injury (SCI). According to different studies, approximately 70% of patients with SCI experience persistent pain. Although previous gene expression profiling studies have been conducted in animal models, gene expression profiling study in human whole blood has not been reported yet. The objective of this study was to define the gene expression profile of neuropathic pain in spinal cord injured patients. Materials and Methods: We performed gene expression analysis including 20.000 genes using Affymetrix GeneChip® Primeview™ Human Gene Expression Arrays. For confirmation of expression levels of selected genes, we performed real time polymerase chain reaction. We gathered samples from periferic blood mononuclear cells. Data of twelve patients with intractable neuropathic pain was compared with thirteen patients who don’t have pain. All patients have complete injuries with a level of injury above T5. Results: A total of 16 differentially expressed genes including 9 up-regulated and 7 down-regulated were obtained with a cut-off degree at 4 fold change. EIF1AY, RPS4Y1, DDX3Y, RPL31, ETS1, KLF3, JUN, CYorf15B, and ERAP2 were in up-regulated and HLA-C, XIST, C4BPA, FAM118A, ZNF506, OVOS2, and C1D were in down-regulated group. KEGG pathway database showed that 14.6% of genes were enriched in the nodes of immune system. Real time polymerase chain reaction analyses did not increase to statistically significant levels for confirmation of gene expression analyze results. Conclusions: Considering these data, findings of this first gene expression study in humans with SCI might provide valuable information for future targets for understanding neuropathic pain pathogenesis. The results of gene expression analyses were not confirmed by real time polymerase chain reaction. Studies with larger sample size are needed for confirmation. This is a cross-sectional study with a control group. Patients were divided into two groups according to intractable neuropathic pain existence.There were 12 patients in group A (Patients with pain) and 13 patients in control group.

Dataset Information

Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord.

Publications

Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord.

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