Gymnastiken är en uppfinning, som, rätt brukad, beröfvar skolungdomen en half timma af frukostlofvet. Detta är dock icke dess enda betydelse, ty gymnastiken stärker äfven blodsystemet, upp- friskar hjertverksamheten, höjer menniskan från jorden (ge- nom trapez), och är mycket lifsfarlig. Svensken Ling var den förste, som upptäckte att ett has- tigt uppsträckande af armarne (eller evenuelt ett vridande till venster af hufvudet), är ett lifsvilkor för hvarje sundt tän- kande menniska. Härefter bildades gymnastikföreningar, som vidare fortplantade denna vackra idé, hvilken för närva- rande är vårt lands stolthet. Den, som skrifvit dessa rader, har endast genom gymnas- tik förvärfvat den fruktansvärda kroppsstyrka, som nu gör det för honom möjligt att med en viss skadeglädje emotse hvarje försök till kritik öfver denna bok. Fakir, F: En hvar sin egen professor List of Papers This thesis is based on the following papers, which are referred to in the text by their Roman numerals. I Peterson M, Elmfeldt D, Svärdsudd K. (2005) Treatment prac- tice in chronic epicondylitis: A survey among general practitio- ners and physiotherapists in Uppsala County, Sweden. Scand J Prim Health Care, 23:239–241. II Peterson M, Butler S, Eriksson M, Svärdsudd K. A randomized controlled trial of exercise versus wait list in chronic tennis el- bow (lateral epicondylosis). Ups J Med Sci in press. III Peterson M, Butler S, Eriksson M, Svärdsudd K. A randomised controlled trial of eccentric versus concentric exercise in chronic tennis elbow (lateral epicondylosis). Submitted. IV Peterson M, Svärdsudd K, Appel L, Engler H, Långström B, Sörensen J. PET-scan shows peripherally increased neurokinin 1 receptor availability in chronic tennis elbow - a picture of neurogenic inflammation? Submitted. Reprints were made with permission from the respective publishers. Contents Prologue ........................................................................................................10 Introduction ...................................................................................................11 Pain ...........................................................................................................11 The history of musculoskeletal pain .........................................................12 Soft tissue musculoskeletal pain ...............................................................12 Tendon pain ..............................................................................................13 Tendinitis versus tendinosis......................................................................13 The pathophysiology of tendinosis ...........................................................14 The substance P – neurokinin 1 receptor system......................................15 Exercise.....................................................................................................16 Tennis Elbow ............................................................................................17 Aims ..............................................................................................................18 Specific aims.............................................................................................18 Study population and methods ......................................................................19 Paper I.......................................................................................................19 Study population...................................................................................19 Methods ................................................................................................19 Papers II and III ........................................................................................19 Study population...................................................................................19 Study design .........................................................................................20 Randomization procedure.....................................................................21 Intervention...........................................................................................21 Data collection......................................................................................22 Paper IV ....................................................................................................26 Study population...................................................................................26 PET examination procedure .................................................................26 Statistical considerations...........................................................................29 Paper I...................................................................................................29 Papers II and III....................................................................................29 Paper IV................................................................................................30 Results ...........................................................................................................31 Paper I.......................................................................................................31 Paper II......................................................................................................32 Baseline characteristics of the study population ..................................32 Analysis of crude outcome data ...........................................................32 Analysis of outcome data adjusted for outcome affecting variables....36 Paper III ....................................................................................................36 Baseline characteristics of the study population ..................................36 Data analysis.........................................................................................36 Paper IV ....................................................................................................39 Baseline characteristics of the study population ..................................39 Neurokinin 1 receptor availability........................................................39 Discussion .....................................................................................................45 Paper I.......................................................................................................45 Papers II and III ........................................................................................46 Paper IV ....................................................................................................48 General discussion ....................................................................................49 Conclusions ...................................................................................................53 Acknowledgements .......................................................................................54 Sammanfattning på svenska..........................................................................56 References .....................................................................................................59 Abbreviations AMPA Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid CI Confidence interval CGRP Calcitonin gene-related peptide CNS Central nervous system DASH Disabilities of the arm, shoulder, hand e.g. exemplia gratia (for example) FGF Fibroblast growth factor fMRI Functional magnetic resonance imaging GP General practitioner GQL Gothenburg quality of life i.e. id est (that is) IGF-1 Insulin-like growth factor 1 IL-1β Interleukin 1 beta MME Maximum muscle elongation MMP Matrix metalloproteinase MVC Maximum voluntary contraction NGF Nerve growth factor NK1 Neurokinin 1 NKA Neurokinin A NMDA N-methyl D-aspartate NSAID Non-steroidal anti-inflammatory drug OSEM Ordered subset expectation maximization PET Positron emission tomography PNS Peripheral nervous system PT Physiotherapist SAS Statistical analysis system SEK The Swedish Krona SBU The Swedish council on technology assessment in health care TE Tennis elbow TENS Transcutaneous electrical nerve stimulation TGF-β Transforming growth factor beta Trk-A Tropomyosin-receptor kinase A TSC Tendon stem cell VAS Visual analogue scale Prologue Early in my professional career in medicine, taking my first, sometimes ra- ther shaky steps as a general practitioner, I was struck by the number of pa- tients consulting me about their aches and pains from tendons, muscles and their skeletal insertions. Often these patients were quite young and the prob- lems seemed to be the result of manual labour. Consulting the literature left me with just about one single diagnosis, tendinitis, implying inflammatory origin, no matter how long the history of the condition was. Injection of steroids or medication with non-steroidal anti-inflammatory drugs, NSAIDs, was to be the cure. When I suggested this treatment to one of my patients, an electrician, on his return visit he gave me a doubtful look. After over a year of work-related pain from tendons he had received steroid injections several times and had taken NSAIDs until gastri- tis became a bigger problem than his tendon pain. Could I really not come up with anything better? It seemed apparent to me, that a long-standing pain condition from ten- dons and muscle insertions could not be treated as an acute inflammatory condition, at least not in the way the textbook suggested according to the presumed pathology of tendinitis. This moment of realization led me on a long