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      Bioinformatics Genes and Pathway Analysis for Chronic Neuropathic Pain after Spinal Cord Injury

      review-article
      1 , 2 , 1 ,
      BioMed Research International
      Hindawi

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          Abstract

          It is well known spinal cord injury (SCI) can cause chronic neuropathic pain (NP); however its underlying molecular mechanisms remain elusive. This study aimed to disclose differentially expressed genes (DEGs) and activated signaling pathways in association with SCI induced chronic NP, in order to identify its diagnostic and therapeutic targets. Microarray dataset GSE5296 has been downloaded from Gene Expression Omnibus (GEO) database. Significant analysis of microarray (SAM), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and pathway network analysis have been used to compare changes of DEGs and signaling pathways between the SCI and sham-injury group. As a result, DEGs analysis showed there were 592 DEGs with significantly altered expression; among them Ccl3 expression showed the highest upregulation which implicated its association with SCI induced chronic NP. Moreover, KEGG analysis found 209 pathways changed significantly; among them the most significantly activated one is MAPK signaling pathway, which is in line with KEGG analysis results. Our results show Ccl3 is highly associated with SCI induced chronic NP; as the exosomes with Ccl3 can be easily and efficiently detected in peripheral blood, Ccl3 may serve as a potential prognostic target for the diagnosis and treatment of SCI induced chronic NP.

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            In silico prediction of protein-protein interactions in human macrophages

            Background: Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages. Results: We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection. Conclusion: Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.
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              P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury.

              Pain after nerve damage is an expression of pathological operation of the nervous system, one hallmark of which is tactile allodynia-pain hypersensitivity evoked by innocuous stimuli. Effective therapy for this pain is lacking, and the underlying mechanisms are poorly understood. Here we report that pharmacological blockade of spinal P2X4 receptors (P2X4Rs), a subtype of ionotropic ATP receptor, reversed tactile allodynia caused by peripheral nerve injury without affecting acute pain behaviours in naive animals. After nerve injury, P2X4R expression increased strikingly in the ipsilateral spinal cord, and P2X4Rs were induced in hyperactive microglia but not in neurons or astrocytes. Intraspinal administration of P2X4R antisense oligodeoxynucleotide decreased the induction of P2X4Rs and suppressed tactile allodynia after nerve injury. Conversely, intraspinal administration of microglia in which P2X4Rs had been induced and stimulated, produced tactile allodynia in naive rats. Taken together, our results demonstrate that activation of P2X4Rs in hyperactive microglia is necessary for tactile allodynia after nerve injury and is sufficient to produce tactile allodynia in normal animals. Thus, blocking P2X4Rs in microglia might be a new therapeutic strategy for pain induced by nerve injury.
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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2017
                15 October 2017
                : 2017
                : 6423021
                Affiliations
                1Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China
                2Cadet Brigade, Third Military Medical University, Chongqing 400038, China
                Author notes

                Academic Editor: Giuseppe Donato

                Author information
                http://orcid.org/0000-0002-2197-9487
                http://orcid.org/0000-0002-9756-5635
                Article
                10.1155/2017/6423021
                5661087
                29164149
                b84c7ea0-6385-4fbe-a532-79ad5adc622d
                Copyright © 2017 Guan Zhang and Ping Yang.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 April 2017
                : 9 August 2017
                : 7 September 2017
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81171719
                Funded by: Chongqing Natural Science of Foundation of China
                Award ID: BB5281
                Categories
                Review Article

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