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      MicroRNA modulation in complex regional pain syndrome

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          Abstract

          Background

          Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification.

          Methods

          We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions.

          Results

          Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs.

          Conclusions

          miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS.

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          Most cited references26

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          GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer.

          Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.
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            Role of the immune system in chronic pain.

            During the past two decades, an important focus of pain research has been the study of chronic pain mechanisms, particularly the processes that lead to the abnormal sensitivity - spontaneous pain and hyperalgesia - that is associated with these states. For some time it has been recognized that inflammatory mediators released from immune cells can contribute to these persistent pain states. However, it has only recently become clear that immune cell products might have a crucial role not just in inflammatory pain, but also in neuropathic pain caused by damage to peripheral nerves or to the CNS.
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              Proposed new diagnostic criteria for complex regional pain syndrome.

              This topical update reports recent progress in the international effort to develop a more accurate and valid diagnostic criteria for complex regional pain syndrome (CRPS). The diagnostic entity of CRPS (published in the International Association for the Study of Pain's Taxonomy monograph in 1994; International Association for the Study of Pain [IASP]) was intended to be descriptive, general, and not imply etiopathology, and had the potential to lead to improved clinical communication and greater generalizability across research samples. Unfortunately, realization of this potential has been limited by the fact that these criteria were based solely on consensus and utilization of the criteria in the literature has been sporadic at best. As a consequence, the full potential benefits of the IASP criteria have not been realized. Consensus-derived criteria that are not subsequently validated may lead to over- or underdiagnosis, and will reduce the ability to provide timely and optimal treatment. Results of validation studies to date suggest that the IASP/CRPS diagnostic criteria are adequately sensitive; however, both internal and external validation research suggests that utilization of these criteria causes problems of overdiagnosis due to poor specificity. This update summarizes the latest international consensus group's action in Budapest, Hungary to approve and codify empirically validated, statistically derived revisions of the IASP criteria for CRPS.
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                Author and article information

                Journal
                J Transl Med
                Journal of Translational Medicine
                BioMed Central
                1479-5876
                2011
                10 November 2011
                : 9
                : 195
                Affiliations
                [1 ]Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
                [2 ]Neurology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
                [3 ]School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA 19104, USA
                Article
                1479-5876-9-195
                10.1186/1479-5876-9-195
                3228853
                22074333
                d271ca12-da46-4050-bf83-67d2eaccaf77
                Copyright ©2011 Orlova et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 September 2011
                : 10 November 2011
                Categories
                Research

                Medicine
                pain,crps,biomarker,microrna
                Medicine
                pain, crps, biomarker, microrna

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