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      Integrated Analysis of Omics Data Reveal AP-1 as a Potential Regulation Hub in the Inflammation-Induced Hyperalgesia Rat Model

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          Abstract

          Inflammation-associated chronic pain is a global clinical problem, affecting millions of people worldwide. However, the underlying mechanisms that mediate inflammation-associated chronic pain remain unclear. A rat model of cutaneous inflammation induced by Complete Freund’s Adjuvant (CFA) has been widely used as an inflammation-induced pain hypersensitivity model. We present the transcriptomics profile of CFA-induced inflammation in the rat dorsal root ganglion (DRG) via an approach that targets gene expression, DNA methylation, and post-transcriptional regulation. We identified 418 differentially expressed mRNAs, 120 differentially expressed microRNAs (miRNAs), and 2,670 differentially methylated regions (DMRs), which were all highly associated with multiple inflammation-related pathways, including nuclear factor kappa B (NF-κB) and interferon (IFN) signaling pathways. An integrated analysis further demonstrated that the activator protein 1 (AP-1) network, which may act as a regulator of the inflammatory response, is regulated at both the transcriptomic and epigenetic levels. We believe our data will not only provide drug screening targets for the treatment of chronic pain and inflammation but will also shed light on the molecular network associated with inflammation-induced hyperalgesia.

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          Most cited references44

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          Multi-omics approaches to disease

          High-throughput technologies have revolutionized medical research. The advent of genotyping arrays enabled large-scale genome-wide association studies and methods for examining global transcript levels, which gave rise to the field of “integrative genetics”. Other omics technologies, such as proteomics and metabolomics, are now often incorporated into the everyday methodology of biological researchers. In this review, we provide an overview of such omics technologies and focus on methods for their integration across multiple omics layers. As compared to studies of a single omics type, multi-omics offers the opportunity to understand the flow of information that underlies disease.
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            Different immune cells mediate mechanical pain hypersensitivity in male and female mice.

            A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling is essential for chronic pain hypersensitivity. Using multiple approaches, we found that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieved similar levels of pain hypersensitivity using adaptive immune cells, likely T lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research.
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              Chronic pain: a review of its epidemiology and associated factors in population-based studies

              Chronic pain is a common, complex, and distressing problem that has a profound impact on individuals and society. It frequently presents as a result of a disease or an injury; however, it is not merely an accompanying symptom, but rather a separate condition in its own right, with its own medical definition and taxonomy. Studying the distribution and determinants of chronic pain allows us to understand and manage the problem at the individual and population levels. Targeted and appropriate prevention and management strategies need to take into account the biological, psychological, socio-demographic, and lifestyle determinants and outcomes of pain. We present a narrative review of the current understanding of these factors.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                28 May 2021
                2021
                : 12
                : 672498
                Affiliations
                [1] 1Department of Anesthesiology, Affiliated Hospital of Nantong University , Nantong, China
                [2] 2The Yancheng Clinical College of XuZhou Medical University, The First People's Hospital of Yancheng , Yancheng, China
                [3] 3Department of Anesthesiology, Qingdao Women and Children’s Hospital , Qingdao, China
                [4] 4Department of Anesthesiology, Suzhou Municipal Hospital Affiliated to Nanjing Medical University , Suzhou, China
                [5] 5Department of Anesthesiology, The First People’s Hospital of Yancheng , Yancheng, China
                [6] 6Graduate School of Nantong University , Nantong, China
                Author notes

                Edited by: Guang-Yin Xu, Soochow University, China

                Reviewed by: Philip Brandon Busbee, University of South Carolina, United States; Shatovisha Dey, Indiana University Hospital, United States

                *Correspondence: Lei Wei, 64624369@ 123456qq.com ; Xiang Zhu, bobofly8850@ 123456sina.com

                This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

                †These authors have contributed equally to this work

                Article
                10.3389/fimmu.2021.672498
                8194263
                34122430
                80ce02a4-696e-4665-be1d-ea4e50274e85
                Copyright © 2021 Zhu, Li, Wang, Su, Wu, Qiu, Zhou, Shan, Wang and Wei

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 February 2021
                : 13 May 2021
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 44, Pages: 11, Words: 4974
                Funding
                Funded by: National Natural Science Foundation of China-Guangdong Joint Fund 10.13039/501100014857
                Categories
                Immunology
                Original Research

                Immunology
                chronic pain,transcriptomic (rna-seq),dna methylation,multi-omics,ap-1
                Immunology
                chronic pain, transcriptomic (rna-seq), dna methylation, multi-omics, ap-1

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