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      Proteomic Analysis of Emodin Treatment in Neuropathic Pain Reveals Dysfunction of the Calcium Signaling Pathway

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          Abstract

          Background

          Neuropathic pain (NP) is a syndrome of pain mediated by distinct pathophysiological processes, and current treatments are not fully satisfactory. Emodin is an effective component of Chinese traditional medicine and has an alleviating effect on NP, but the pharmacological mechanism is not clear.

          Methods

          We used isobaric tags for relative and absolute quantitation (iTRAQ) technique integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify potential targets of emodin in a rat peripheral nerve chronic constriction injury (CCI) model.

          Results

          A total of 177 differentially expressed proteins were identified among the sham group, CCI group, and emodin group, with a threshold of 1.2-fold change and a P value ≤ 0.05. Among them, 100 differentially expressed proteins (51 up-regulated and 49 down-regulated) were identified in the CCI group compared with sham group. Moreover, 108 differentially expressed proteins (65 up-regulated and 43 down-regulated) were identified in the emodin group with the CCI group as reference. The enrichment analysis of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed an important role of calcium signaling pathway, neurotransmitter regulation, and long-term potentiation (LTP) in emodin-treated CCI model. Real-time quantitative fluorescence PCR (qRT-PCR) and Western blot analysis revealed that emodin decreased expression of calcium signaling related proteins, including calmodulin (CaM) dependent protein kinase II (CaMK II), phospholipase Cβ1 (PLCβ1), protein kinase C (PKC), protein kinase C (PKA), and tropomyosin-related kinase B (TrkB), compared with the CCI group.

          Conclusion

          Overall, these findings indicated that emodin might alleviate NP by regulating the calcium signaling pathway.

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          Most cited references 28

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          clusterProfiler: an R package for comparing biological themes among gene clusters.

          Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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            A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man

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              Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis.

              New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                jpr
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                05 March 2021
                2021
                : 14
                : 613-622
                Affiliations
                [1 ]Basic Medical School, Guizhou University of Traditional Chinese Medicine , Guiyang, Guizhou, People’s Republic of China
                [2 ]First Clinical Medical School, Guangzhou University of Chinese Medicine , Guangzhou, Guangdong, People’s Republic of China
                Author notes
                Correspondence: Zhibing Wu Department of Neurology, First Clinical Medical College of Guangzhou University of Chinese Medicine , 12 Jichang Road, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 020 36585577 Email wuzhibing2021@126.com
                Article
                290681
                10.2147/JPR.S290681
                7943569
                © 2021 Chen et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 5, Tables: 1, References: 29, Pages: 10
                Funding
                Funded by: National Natural Science Fund;
                The present study was supported in part by a grant from National Natural Science Fund (nos.81373571).
                Categories
                Original Research

                Anesthesiology & Pain management

                kegg, neuropathic pain, itraq, cci, emodin

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