Skip to main content

GENERAL COMMENTARY article

Front. Aging Neurosci., 21 March 2017
Sec. Neurocognitive Aging and Behavior

Commentary: Role of VEGF, Nitric Oxide, and Sympathetic Neurotransmitters in the Pathogenesis of Tendinopathy: A Review of the Current Evidences

  • Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, University of Oxford, Oxford, UK

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.

References

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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.

PubMed Abstract | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

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

PubMed Abstract | CrossRef Full Text | Google Scholar

Keywords: tendinopathy, inflammation, glutamates, pain, VEGF, NMDAR, tendons

Citation: Dean BJF (2017) Commentary: Role of VEGF, Nitric Oxide, and Sympathetic Neurotransmitters in the Pathogenesis of Tendinopathy: A Review of the Current Evidences. Front. Aging Neurosci. 9:60. doi: 10.3389/fnagi.2017.00060

Received: 07 September 2016; Accepted: 28 February 2017;
Published: 21 March 2017.

Edited by:

Aurel Popa-Wagner, University of Rostock, Germany

Reviewed by:

Paul W. Ackermann, Karolinska University Hospital, Sweden

Copyright © 2017 Dean. 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) or licensor 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.

*Correspondence: Benjamin J. F. Dean, bendean1979@gmail.com

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.