title: The sympathetic nervous system and tendinopathy: a systematic review.
abstract: BACKGROUND
  Tendinopathy is a clinical diagnosis of localised tendon pain often confirmed by imaging findings. The pathophysiological cause of the pain is unknown and the sympathetic nervous system (SNS) may be implicated.
  
  
  OBJECTIVE
  To review what is known regarding the role of the SNS in human tendinopathy.
  
  
  METHODS
  Published data describing sympathetic innervation or an index of sympathetic activity in human tendons were eligible for inclusion.
  
  
  METHODS
  Bibliographical databases (AMED, Biological Abstracts, CINAHL Plus, EMBASE, MEDLINE, Scopus, SPORTDiscus and Web of Science) were searched for relevant articles. Reference lists from included articles were screened for additional articles.
  
  
  METHODS
  Studies were scored with a quality assessment tool to identify potential sources of bias. Each question had an explicit decision rule to guide assessment.
  
  
  RESULTS
  Nine case-control and four cross-sectional studies examined sympathetic innervation of tendons. There was evidence suggesting a lack of difference in sympathetic innervation of tendon proper between tendinopathy biopsies and healthy controls. In contrast, the paratendinous tissue showed evidence of increased sympathetic innervation in painful tendons. The most notable increase in SNS markers was seen in abnormal tenocytes from painful tendons. Data from two studies were suitable for meta-analysis. These heterogeneous studies revealed no difference in sympathetic innervation between painful and pain-free tendons. No studies recorded SNS activity in vivo.
  
  
  CONCLUSIONS
  Sympathetic innervation in painful tendons depends on tissue type. Abnormal tenocytes may have increased capacity for self-production of sympathetic neurotransmitters. Future insight may be gained by measuring global in vivo sympathetic drive in tendinopathy.
authors: Central Medical School, Monash University, Melbourne, VIC, Australia, jljew3@student.monash.edu.
authors: Jacob L
authors: JL
authors: Jewson
authors: Gavin W
authors: GW
authors: Lambert
authors: Michael
authors: M
authors: Storr
authors: James E
authors: JE
authors: Gaida
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D020078:Neurogenic Inflammation / Q000503:physiopathology; D009478:Neuropeptide Y / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D052256:Tendinopathy / Q000503:physiopathology*; D013710:Tendons / Q000166:cytology / Q000294:innervation; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009478:Neuropeptide Y; D014446:Tyrosine 3-Monooxygenase
references: Knee Surg Sports Traumatol Arthrosc. 2011 Aug;19(8):1367-75
references: 21567177
references: Ann Acad Med Singapore. 1993 Jul;22(4):646-50
references: 7504903
references: Pain. 1995 Oct;63(1):11-20
references: 8577481
references: Pharmacol Rev. 1985 Dec;37(4):333-64
references: 3915090
references: Sports Med. 2014 Jan;44(1):9-23
references: 24027089
references: Clin Sci (Lond). 1985 Nov;69(5):533-40
references: 4053509
references: Radiology. 1996 Sep;200(3):821-7
references: 8756939
references: J Epidemiol Community Health. 1998 Jun;52(6):377-84
references: 9764259
references: J Hypertens. 1988 Jun;6(6):481-8
references: 3411126
references: J Mol Cell Cardiol. 1989 Mar;21(3):279-90
references: 2568493
references: J Leukoc Biol. 2005 Dec;78(6):1215-22
references: 16204636
references: Adv Enzymol Relat Areas Mol Biol. 1995;70:103-220
references: 8638482
references: J Bone Joint Surg Am. 2005 Jul;87(7):1580-3
references: 15995126
references: J Rheumatol. 1990 Jul;17(7):951-2
references: 2213763
references: Neuroscience. 1991;45(3):761-5
references: 1723182
references: Med Sci Sports Exerc. 2009 Jun;41(6):1194-7
references: 19461549
references: J Orthop Sci. 2013 Mar;18(2):238-44
references: 23306538
references: Foot Ankle Int. 2008 May;29(5):498-501
references: 18510903
references: Am J Physiol. 1994 Jun;266(6 Pt 2):H2508-14
references: 8024012
references: Scand J Med Sci Sports. 2014 Oct;24(5):773-8
references: 23600756
references: Rheumatology (Oxford). 2002 Oct;41(10):1155-62
references: 12364636
references: J Orthop Res. 2004 Mar;22(2):334-8
references: 15013093
references: J Biomech. 2004 Jun;37(6):865-77
references: 15111074
references: Clin Sci (Lond). 1997 Mar;92(3):285-9
references: 9093009
references: Physiol Rev. 1990 Oct;70(4):963-85
references: 1977182
references: Hypertension. 1988 Jan;11(1):3-20
references: 2828236
references: Am J Hypertens. 1997 Jan;10(1):77-83
references: 9008251
references: Vet Pathol. 2014 Jan;51(1):42-87
references: 24129895
references: Clin Biomech (Bristol, Avon). 2010 Jun;25(5):476-82
references: 20193974
references: Clin Rheumatol. 2003 Sep;22(3):229-33
references: 14505217
references: Knee Surg Sports Traumatol Arthrosc. 2007 Oct;15(10 ):1272-9
references: 17604979
references: Neuromolecular Med. 2008;10(3):141-7
references: 17990126
references: Arthroscopy. 1998 Nov-Dec;14(8):840-3
references: 9848596
references: Am J Sports Med. 2009 Sep;37(9):1855-67
references: 19188560
references: Sports Med. 1999 Jun;27(6):393-408
references: 10418074
references: Cell Tissue Res. 2008 Feb;331(2):385-400
references: 17999088
references: Microsc Res Tech. 2007 Oct;70(10):908-11
references: 17661370
references: Physiol Rev. 1979 Oct;59(4):919-57
references: 227005
references: Ann Rheum Dis. 1991 Nov;50(11):747-51
references: 1722965
references: Br J Sports Med. 2012 Mar;46(3):163-8
references: 22113234
references: Ann Rheum Dis. 2005 Jul;64(7):1083-6
references: 15958764
references: Foot Ankle Int. 1997 Sep;18(9):565-9
references: 9310767
references: Diabete Metab. 1994 Nov-Dec;20(6):513-21
references: 7713273
references: Knee Surg Sports Traumatol Arthrosc. 2008 Jun;16(6):621-6
references: 18418576
references: Muscle Nerve. 2007 Nov;36(5):595-614
references: 17623856
references: Auton Autacoid Pharmacol. 2002 Jun;22(3):177-86
references: 12452903
references: J Hand Surg Am. 2007 May-Jun;32(5):597-605
references: 17481995
references: J Hypertens. 1998 Nov;16(11):1635-9
references: 9856364
references: BMC Med Res Methodol. 2003 Nov 10;3:25
references: 14606960
references: Hypertension. 1989 Aug;14(2):177-83
references: 2759678
references: Metabolism. 2008 Oct;57(10):1422-7
references: 18803948
references: Pain. 1992 Apr;49(1):9-12
references: 1594285
references: J Neurosci Res. 1985;13(3):453-9
references: 3921721
references: Clin Sports Med. 2003 Oct;22(4):675-92
references: 14560540
references: Cochrane Database Syst Rev. 2011 Mar 16;(3):CD003525
references: 21412883
references: J Exp Biol. 2005 Dec;208(Pt 24):4715-25
references: 16326953
references: Cells Tissues Organs. 1999;165(1):45-54
references: 10460973
references: Microsc Res Tech. 2006 Oct;69(10):808-19
references: 16830327
references: Clin J Sport Med. 2006 Sep;16(5):388-91
references: 17016113
references: J Appl Physiol (1985). 2005 Apr;98(4):1379-86
references: 15591297
references: Clin Orthop Relat Res. 1995 Jul;(316):151-64
references: 7634699
references: J Orthop Res. 2002 Jul;20(4):849-56
references: 12168677
references: J Occup Environ Hyg. 2005 Apr;2(4):203-12
references: 15788381
references: Knee Surg Sports Traumatol Arthrosc. 1999;7(6):378-81
references: 10639657
references: Br J Sports Med. 2007 Jun;41(6):e3
references: 17035479
references: J Int Med Res. 2008 May-Jun;36(3):505-11
references: 18534132
references: Clin Neurophysiol. 2006 Nov;117(11):2357-84
references: 16904937
references: Clin J Sport Med. 2005 May;15(3):133-5
references: 15867554
references: J Clin Epidemiol. 2008 Apr;61(4):344-9
references: 18313558
references: J Orthop Res. 2001 May;19(3):372-8
references: 11398848
references: Clin Biomech (Bristol, Avon). 2005 Jun;20(5):532-9
references: 15836941
references: Histol Histopathol. 2008 Feb;23 (2):197-208
references: 17999376
references: Am J Sports Med. 2000 Sep-Oct;28(5):634-42
references: 11032217
references: J Orthop Sci. 2013 Jul;18(4):528-35
references: 23674348
references: Microsc Res Tech. 2007 Apr;70(4):310-24
references: 17206652
references: Am J Physiol Cell Physiol. 2004 Oct;287(4):C912-8
references: 15201139
references: Br J Sports Med. 2009 Apr;43(4):269-75
references: 19155232
references: Br J Sports Med. 2009 Dec;43(14):1136-42
references: 19364758
references: J Rheumatol. 2006 Jul;33(7):1351-63
references: 16821270
references: Bull Hosp Jt Dis. 1996;54(4):236-40
references: 8731417
references: Cochrane Database Syst Rev. 2009 Jul 08;(3):CD006355
references: 19588386
references: Clin Exp Neurol. 1989;26:45-50
references: 2484453
references: Knee Surg Sports Traumatol Arthrosc. 2011 May;19(5):835-41
references: 21222102
references: Am J Physiol. 1989 Jan;256(1 Pt 2):H105-10
references: 2912172
references: Phys Sportsmed. 2000 May;28(5):38-48
references: 20086639
references: Neuroscience. 1993 Aug;55(4):1037-43
references: 8232896
references: Am J Sports Med. 2006 Nov;34(11):1801-8
references: 16816149
references: Clin Orthop Relat Res. 2013 Sep;471(9):3036-46
references: 23609815
references: Clin J Pain. 2000 Jun;16(2 Suppl):S12-20
references: 10870735
references: Essays Biochem. 1995;30:15-35
references: 8822146
references: J Hand Surg Am. 1995 Jan;20(1):109-14
references: 7722249