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.
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Conflict of interest
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References
1
AnderssonG.DanielsonP.AlfredsonH.ForsgrenS. (2008). Presence of substance P and the neurokinin-1 receptor in tenocytes of the human Achilles tendon. Regul. Pept.150, 81–87. 10.1016/j.regpep.2008.02.005
2
DakinS. G.MartinezF. O.YappC.WellsG.OppermannU.DeanB. J. F.et al. (2015). Inflammation activation and resolution in human tendon disease. Sci. Transl. Med.7, 311ra173. 10.1126/scitranslmed.aac4269
3
DeanB. J.FranklinS. L.MurphyR. J.JavaidM. K.CarrA. 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. 10.1136/bjsports-2013-093178
4
DeanB. J.GettingsP.DakinS. G.CarrA. J. (2016). Are inflammatory cells increased in painful human tendinopathy? A systematic review. Br. J. Sports Med.50, 216–220. 10.1136/bjsports-2015-094754
5
DeanB. J.SnellingS. J.DakinS. G.JavaidM. K.CarrA. 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.
6
DeanB. J. F.SnellingS. J. B.DakinS. G.MurphyR. J.JavaidM. K.CarrA. 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. 10.1186/s13075-015-0691-5
7
ForsgrenS.DanielsonP.AlfredsonH. (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. 10.1016/j.regpep.2004.09.008
8
FranklinS. L.DeanB. J.WhewayK.WatkinsB.JavaidM. K.CarrA. J. (2014). Up-regulation of glutamate in painful human supraspinatus tendon tears. Am. J. Sports Med.42, 1955–1962. 10.1177/0363546514532754
9
GotohM.HamadaK.YamakawaH.InoueA.FukudaH. (1998). Increased substance P in subacromial bursa and shoulder pain in rotator cuff diseases. J. Orthopaed. Res.16, 618–621. 10.1002/jor.1100160515
10
LakemeierS.ReicheltJ. J.PatzerT.Fuchs-WinkelmannS.PalettaJ. R.SchoferM. 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. 10.1186/1471-2474-11-230
11
MillarN. L.ReillyJ. H.KerrS. C.CampbellA. L.LittleK. J.LeachW. J.et al. (2012). Hypoxia: a critical regulator of early human tendinopathy. Ann. Rheum. Dis.71, 302–310. 10.1136/ard.2011.154229
12
ShindleM. K.ChenC. C. T.RobertsonC.DiTullioA. E.PaulusM. C.ClintonC. 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. 10.1016/j.jse.2011.02.015
13
VastaS.Di MartinoA.ZampognaB.TorreG.PapaliaR.DenaroV. (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. 10.3389/fnagi.2016.00186
Summary
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
Volume
9 - 2017
Edited by
Aurel Popa-Wagner, University of Rostock, Germany
Reviewed by
Paul W. Ackermann, Karolinska University Hospital, Sweden
Updates
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
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