A commentary on
Role of VEGF, Nitric Oxide, and Sympathetic Neurotransmitters in the Pathogenesis of Tendinopathy: A Review of the Current Evidences
by Vasta, S., Di Martino, A., Zampogna, B., Torre, G., Papalia, R., and Denaro, V. (2016). Front. Aging Neurosci. 8:186. doi: 10.3389/fnagi.2016.00186
I read the recent systematic review which asked some interesting questions regarding the pathogenesis of tendinopathy (Vasta et al., 2016). The statement “histologic studies have demonstrated the absence of inflammatory infiltrates” is not supported by the current evidence base. Our recent systematic review on this subject demonstrated that the absence of neutrophils does not equate to the absence of inflammatory cells (Dean et al., 2016), while several recent studies have provided compelling evidence to support the hypothesis that chronic inflammation is a key factor in the pathogenesis of tendinopathy (Dakin et al., 2015; Dean et al., 2015a). In addition the search strategy does not appear to have been comprehensive. We have carried out a number of systematic reviews in this area (Dean et al., 2016; Vasta et al., 2016) which identified numerous studies which have been missed by this review (Gotoh et al., 1998; Forsgren et al., 2005; Andersson et al., 2008; Lakemeier et al., 2010; Shindle et al., 2011; Millar et al., 2012). We have also published several pieces of work related to markers such as VEGF, glutamate, various glutamate receptors, the neurokinin-1 receptor and tyrosine hydroxylase which were also not included (Dean et al., 2014, 2015a,b; Franklin et al., 2014). It is rather problematic that so many relevant studies have not been incorporated into this systematic review. It is important that readers are fully informed of the current evidence base and thus can be made aware of the role of neuro-inflammatory change in the pathogenesis of tendinopathy.
Author Contributions
The author confirms being the sole contributor of this work and approved it for publication.
Conflict of Interest Statement
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Andersson, G., Danielson, P., Alfredson, H., and Forsgren, S. (2008). Presence of substance P and the neurokinin-1 receptor in tenocytes of the human Achilles tendon. Regul. Pept. 150, 81–87. doi: 10.1016/j.regpep.2008.02.005
Dakin, S. G., Martinez, F. O., Yapp, C., Wells, G., Oppermann, U., Dean, B. J. F., et al. (2015). Inflammation activation and resolution in human tendon disease. Sci. Transl. Med. 7, 311ra173. doi: 10.1126/scitranslmed.aac4269
Dean, B. J., Franklin, S. L., Murphy, R. J., Javaid, M. K., and Carr, A. J. (2014). Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy? Br. J. Sports Med. 48, 1620–1626. doi: 10.1136/bjsports-2013-093178
Dean, B. J., Gettings, P., Dakin, S. G., and Carr, A. J. (2016). Are inflammatory cells increased in painful human tendinopathy? A systematic review. Br. J. Sports Med. 50, 216–220. doi: 10.1136/bjsports-2015-094754
Dean, B. J., Snelling, S. J., Dakin, S. G., Javaid, M. K., and Carr, A. J. (2015b). In vitro effects of glutamate and N-methyl-D-aspartate receptor (NMDAR) antagonism on human tendon derived cells. J. Orthopaed. Res. 33, 1515–1522.
Dean, B. J. F., Snelling, S. J. B., Dakin, S. G., Murphy, R. J., Javaid, M. K., and Carr, A. J. (2015a). Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy. Arthritis Res. Ther. 17:176. doi: 10.1186/s13075-015-0691-5
Forsgren, S., Danielson, P., and Alfredson, H. (2005). Vascular NK-1 receptor occurrence in normal and chronic painful Achilles and patellar tendons: studies on chemically unfixed as well as fixed specimens. Regul. Pept. 126, 173–181. doi: 10.1016/j.regpep.2004.09.008
Franklin, S. L., Dean, B. J., Wheway, K., Watkins, B., Javaid, M. K., and Carr, A. J. (2014). Up-regulation of glutamate in painful human supraspinatus tendon tears. Am. J. Sports Med. 42, 1955–1962. doi: 10.1177/0363546514532754
Gotoh, M., Hamada, K., Yamakawa, H., Inoue, A., and Fukuda, H. (1998). Increased substance P in subacromial bursa and shoulder pain in rotator cuff diseases. J. Orthopaed. Res.16, 618–621. doi: 10.1002/jor.1100160515
Lakemeier, S., Reichelt, J. J., Patzer, T., Fuchs-Winkelmann, S., Paletta, J. R., and Schofer, M. D. (2010). The association between retraction of the torn rotator cuff and increasing expression of hypoxia inducible factor 1alpha and vascular endothelial growth factor expression: an immunohistological study. BMC Musculoskelet. Disord. 11:230. doi: 10.1186/1471-2474-11-230
Millar, N. L., Reilly, J. H., Kerr, S. C., Campbell, A. L., Little, K. J., Leach, W. J., et al. (2012). Hypoxia: a critical regulator of early human tendinopathy. Ann. Rheum. Dis. 71, 302–310. doi: 10.1136/ard.2011.154229
Shindle, M. K., Chen, C. C. T., Robertson, C., DiTullio, A. E., Paulus, M. C., Clinton, C. M., et al. (2011). Full-thickness supraspinatus tears are associated with more synovial inflammation and tissue degeneration than partial-thickness tears. J. Shoul. Elbow Surg. Am. Shoul. Elbow Surg. 20, 917–927. doi: 10.1016/j.jse.2011.02.015
Vasta, S., Di Martino, A., Zampogna, B., Torre, G., Papalia, R., and Denaro, V. (2016). Role of VEGF, Nitric Oxide, and sympathetic neurotransmitters in the pathogenesis of tendinopathy: a review of the current evidences. Front. Aging Neurosci. 8:186. doi: 10.3389/fnagi.2016.00186
Benjamin J. F. Dean*
* Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK
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Abstract
Glucocorticoids induce specific ion-channel-mediated toxicity in human rotator cuff tendon: a mechanism underpinning the ultimately deleterious effect of steroid injection in tendinopathy? Differences in glutamate receptors and inflammatory cell numbers are associated with the resolution of pain in human rotator cuff tendinopathy. The association between retraction of the torn rotator cuff and increasing expression of hypoxia inducible factor 1alpha and vascular endothelial growth factor expression: an immunohistological study.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer