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      Emerging roles of long non‐coding RNAs in neuropathic pain

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          Abstract

          Neuropathic pain, a type of chronic and potentially disabling pain resulting from primary injury/dysfunction of the somatosensory nervous system and spinal cord injury, is one of the most intense types of chronic pain, which incurs a significant economic and public health burden. However, our understanding of its cellular and molecular pathogenesis is still far from complete. Long non‐coding RNAs (lncRNAs) are important regulators of gene expression and have recently been characterized as key modulators of neuronal functions. Emerging evidence suggested that lncRNAs are deregulated and play pivotal roles in the development of neuropathic pain. This review summarizes the current knowledge about the roles of deregulated lncRNAs (eg, KCNA2‐AS, uc.48+, NONRATT021972, MRAK009713, XIST, CCAT1) in the development of neuropathic pain. These studies suggested that specific regulation of lncRNAs or their downstream targets might provide novel therapeutic avenues for this refractory disease.

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          Most cited references45

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          Mechanisms of neuropathic pain.

          Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, "channelopathies," and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms. Neuropathic pain reflects both peripheral and central sensitization mechanisms. Abnormal signals arise not only from injured axons but also from the intact nociceptors that share the innervation territory of the injured nerve. This review focuses on how both human studies and animal models are helping to elucidate the mechanisms underlying these surprisingly common disorders. The rapid gain in knowledge about abnormal signaling promises breakthroughs in the treatment of these often debilitating disorders.
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            The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

            Abstract Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene–related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.
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              Cell cycle regulation by long non-coding RNAs

              The mammalian cell cycle is precisely controlled by cyclin-dependent kinases (CDKs) and related pathways such as the RB and p53 pathways. Recent research on long non-coding RNAs (lncRNAs) indicates that many lncRNAs are involved in the regulation of critical cell cycle regulators such as the cyclins, CDKs, CDK inhibitors, pRB, and p53. These lncRNAs act as epigenetic regulators, transcription factor regulators, post-transcription regulators, and protein scaffolds. These cell cycle-regulated lncRNAs mainly control cellular levels of cell cycle regulators via various mechanisms, and may provide diversity and reliability to the general cell cycle. Interestingly, several lncRNAs are induced by DNA damage and participate in cell cycle arrest or induction of apoptosis as DNA damage responses. Therefore, deregulations of these cell cycle regulatory lncRNAs may be involved in tumorigenesis, and they are novel candidate molecular targets for cancer therapy and diagnosis.
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                Author and article information

                Contributors
                lishugangpumc@163.com
                Journal
                Cell Prolif
                Cell Prolif
                10.1111/(ISSN)1365-2184
                CPR
                Cell Proliferation
                John Wiley and Sons Inc. (Hoboken )
                0960-7722
                1365-2184
                25 October 2018
                January 2019
                : 52
                : 1 ( doiID: 10.1111/cpr.2019.52.issue-1 )
                : e12528
                Affiliations
                [ 1 ] Department of Orthopaedic Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
                [ 2 ] Department of Orthopedic Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University Jishuitan Orthopaedic College of Tsinghua University Beijing China
                [ 3 ] Department of Anaesthesia and Intensive Care The Chinese University of Hong Kong Hong Kong Hong Kong Special Administrative Region Hong Kong
                [ 4 ] State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences The Chinese University of Hong Kong Hong Kong Hong Kong Special Administrative Region Hong Kong
                Author notes
                [*] [* ] Correspondence

                Shugang Li, Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

                Email: lishugangpumc@ 123456163.com

                Author information
                http://orcid.org/0000-0001-6024-0194
                Article
                CPR12528
                10.1111/cpr.12528
                6430490
                30362191
                cfa2a8b1-2c29-4012-98e0-f838605ead5b
                © 2018 The Authors Cell Proliferation Published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 July 2018
                : 01 August 2018
                : 28 August 2018
                Page count
                Figures: 1, Tables: 2, Pages: 7, Words: 11776
                Funding
                Funded by: health improvement and research
                Award ID: 2016–1–4096
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                cpr12528
                January 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.5 mode:remove_FC converted:05.07.2019

                Cell biology
                diabetic peripheral neuropathy,lncrnas,nerve pain,neuroinflammation,spinal cord pain
                Cell biology
                diabetic peripheral neuropathy, lncrnas, nerve pain, neuroinflammation, spinal cord pain

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