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      Increased nerve growth factor expression in the synovial tissues of patients with rotator cuff tears

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          Abstract

          Background

          Rotator cuff tears (RCTs) are often associated with severe shoulder pain. Non-steroidal anti-inflammatory drugs, not recommended for long-term use, do not effectively manage RCT-induced pain, resulting in reduced quality of life. To improve management, a better understanding of the fundamental properties of RCT pain is needed. Here, we aimed to compare the expression levels of nerve growth factor (NGF) and cyclooxygenase-2 (COX-2) mRNA in the synovial tissues of patients with RCT-induced pain and patients with non-painful recurrent shoulder dislocation (RSD).

          Methods

          The study included 32 patients with RCT who underwent arthroscopic rotator cuff repair and 28 patients with non-painful RSD who underwent arthroscopic Bankart repair. Synovial tissue samples were harvested from subacromial bursa and rotator interval of RCT patients and from the rotator interval of RSD patients. Samples were analyzed quantitatively expression levels for NGF and COX2 mRNA and NGF protein.

          Results

          NGF mRNA and protein levels were significantly higher in the rotator interval of RCT patients than in the rotator interval of RSD patients ( p = 0.0017, p = 0.012, respectively), while COX2 mRNA levels did not differ significantly between the two patient groups. In RCT patients, COX2 mRNA was more highly expressed in the rotator interval than in the subacromial bursa ( p = 0.038), whereas the mRNA and protein levels of NGF did not differ between the two tissues. The expression of NGF mRNA in the synovium of the rotator interval was significantly correlated with the numeric rating scale of pain (ρ = 0.38, p = 0.004).

          Conclusion

          NGF mRNA and protein levels were elevated in patients with painful RCT compared with those in patients with non-painful RSD, whereas COX-2 levels were comparable in the two patient groups. These findings provide insights into novel potential strategies for clinical management of RCT.

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          Most cited references51

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          Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

          The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data. Copyright 2001 Elsevier Science (USA).
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            A Clinical Method of Functional Assessment of the Shoulder

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              Prevalence and risk factors of a rotator cuff tear in the general population.

              Little information is available about the epidemiology of rotator cuff tears in a population-based study. The purpose of this study was to elucidate the true prevalence of rotator cuff tears regardless of the presence or absence of symptoms in the general population and to assess the relationship between tears and their backgrounds. A medical check-up was conducted for residents of a mountain village in Japan. The subjects consisted of 683 people (total of 1,366 shoulders), including 229 males and 454 females with a mean age of 57.9 years (range, 22-87). We examined their background factors, physical examinations and ultrasonographic examinations on both shoulders. Rotator cuff tears were present in 20.7% and the prevalence increased with age. Thirty-six percent of the subjects with current symptoms had rotator cuff tears, while 16.9% of the subjects without symptoms also had rotator cuff tears. Rotator cuff tears in the general population were most commonly associated with elderly patients, males, affected the dominant arm, engaged in heavy labor, having a history of trauma, positive for impingement sign, showed lesser active forward elevation and weaker muscle strength in abduction and external rotation. A logistic regression analysis revealed the risk factors for a rotator cuff tear to be a history of trauma, dominant arm and age. 20.7% of 1,366 shoulders had full-thickness rotator cuff tears in the general population. The risk factors for rotator cuff tear included a history of trauma, dominant arm and age. Level 3.
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                Author and article information

                Journal
                Mol Pain
                Mol Pain
                MPX
                spmpx
                Molecular Pain
                SAGE Publications (Sage CA: Los Angeles, CA )
                1744-8069
                1 June 2021
                2021
                : 17
                : 17448069211021252
                Affiliations
                [1 ]Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, Japan
                [2 ]Department of Health Science and Technology, Center for Neuroplasticity and Pain, School of Medicine, Aalborg University, Aalborg, Denmark
                [3 ]Department of Pathology, Kitasato University School of Medicine, Sagamihara, Japan
                [4 ]Department of Rehabilitation, Kitasato University School of Medicine, Sagamihara, Japan
                Author notes
                [*]Tomonori Kenmoku, Department of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa 252-0374, Japan. Email: pseudolefty811@ 123456yahoo.co.jp
                Author information
                https://orcid.org/0000-0002-2664-7377
                https://orcid.org/0000-0001-8423-5357
                Article
                10.1177_17448069211021252
                10.1177/17448069211021252
                8175831
                34074169
                bde5ee45-0771-41e5-a991-7597f04d0bef
                © The Author(s) 2021

                Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 29 November 2020
                : 12 April 2021
                : 6 May 2021
                Funding
                Funded by: Danish National Research Foundation;
                Award ID: DNRF121
                Funded by: the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research (KAKENHI) program;
                Award ID: 18K16633
                Categories
                Research Article
                Custom metadata
                January-December 2021
                ts2

                Molecular medicine
                nerve growth factor,cyclooxygenase-2,rotator cuff tears,recurrent shoulder dislocation

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