This blog is an amended version of an essay first published in the McKenzie Institute Mechanical Diagnosis and Therapy Practitioners (MIMDTP) UK Newsletter. It also represents some of my early work leading to the start of my PhD in 2016. So I would like to acknowledge and thank my supervisors Pip Logan and Paul Hendrick, and collaborators Marcus Bateman, Chris Littlewood, Fiona Moffatt, Michael Rathleff, James Selfe and Toby Smith.
Leslie is 19 years old and presents at the clinic with an insidious onset of anterior knee pain. She doesn’t quite remember when it started but states that it started 2 or 3 years ago. Leslie has diffuse anterior knee pain during stair walking, bicycling to university, and when she tries to run. Consequently, she now no longer does any regular exercise. She was later diagnosed with patellofemoral pain (PFP) by the physiotherapist.
Patellofemoral pain (PFP) is a common musculoskeletal (MSK) disorder and one of the most common reasons why adolescents and young adults seek medical help with 1 in 6 suffering at any one time [1,2]. The main symptoms include retropatella pain, or diffuse peripatellar pain, aggravated by activities that load the patellofemoral joint such as climbing and descending stairs, squatting and sitting with prolonged knee flexion [3–5]. Other symptoms include patella crepitus and giving way sensations [6–8].
Despite the implementation of evidence-based treatment, including exercise therapy, the long-term prognosis for PFP is still poor, with only one third being pain-free, one year after the initial diagnosis . Patients who complain of high base levels and pain and a longer duration of symptoms typically have the most unfavourable recovery .
The Chartered Society of Physiotherapy, UK (CSP) has ranked PFP the 3rd most important topic out of 185 in their Musculoskeletal Research Priority Project .
Recent findings have led us to evolve the thinking of patellofemoral pain. Once we thought it was only about the knee itself. Then we started to discover the importance of the foot, hip and trunk. This led to ‘sub-grouping’, which has been highlighted as a research priority to investigate the effectiveness of targeted treatments based upon a classification system . To date, no large randomised controlled trial has been published, but currently, this approach is being investigated . However, now it appears that we should perhaps broaden our perspective even more and re-examine relevant current evidence surrounding different models of pain mechanisms and the development of PFP. This blog will look at this and some of the underpinning theoretical effects of exercise intervention and put forward a rationale for a different approach.
Tissue Pathology Models of Pain:
There is no consensus on the mechanisms that cause PFP  but it seems likely that the cause is multifactorial and includes loading of the patellofemoral joint . Tissue-based pathology models have suggested various risk factors such as general muscle weakness , soft tissue tightness , lower limb structural abnormalities , movement dysfunction  and quadriceps mal-timing . These MSK abnormalities are often assumed to affect the patella alignment or kinematics, resulting in greater stress between the patella and femur and the development of pain and dysfunction [14,20–22]. Despite positive results with exercise therapy, patients kinematics and assumed ‘alignment dysfunction’ at the knee or patella typically remain unchanged , questioning the role of such anatomical structures in patients with PFP.
Usual physiotherapy typically involves exercises and treatments aimed at reducing pain and restoring the assumed patella malalignment [20,21]. These include strengthening and stretching exercises, taping, and foot orthoses .
Reviews of taping and foot orthoses conclude that there is limited evidence for their long term effectiveness in pain when combined with exercises, compared to exercise alone [21,25,26]. Taping has shown some benefit in terms of short term pain reduction, and it is it thought current best practice to tailor the application to control specific patella movement, i.e. lateral tilt, glide and spin . There does however remain some debate over the inter-rater reliability of assessing patella position and Q-angle[27,28], and the effect taping has on patella alignment and position , which suggests that any taping application cannot truly be specific. It is thought by the current authors that potential mechanisms behind short term taping efficacy could be attributed to central pain processes via an enhancement of proprioceptive feedback .
A recent review of exercise therapy reported strong evidence existed for exercise therapy over no treatment, particularly with strengthening exercises . Although there remains some debate over whether hip or knee strength exercises are superior Peters and Tyson (2013) reported hip strengthening is superior, while Papadopoulos et al. (2015) reported knee extension exercises were superior. These findings are supported by a systematic review in 2012 looking into the risk factors associated with PFP; they included seven studies with a total of 135 variables which only found evidence for having weak knee extension and being female as a risk factor for developing PFP . Another review reported that reduced hip strength is likely a result of PFP but not part of the risk factors associated with the development of PFP . Both further questioning the role of anatomical structures with the development of PFP.
There remains some debate over the role of anatomical variations/dysfunction in the development of PFP with a lack of association between structural changes and pain . Structural changes do not fully explain the positive response to therapeutic exercise, and structural pathology resulting in nocioceptive input with a pain response seem inadequate for PFP.
ROLE OF CENTRAL NERVOUS SYSTEM:
Traditional pain models that describe tissue pathology as a source of nocioceptive input and a pain response have been insufficient in the assessment and treatment of PFP. Other models reconceptualise pain and put forward concepts that are based upon the premise that pain does not provide a measure of the state of tissue, that it is modulated by many factors, and the relationship between pain and tissue becomes less predictable the longer pain persists . Known as central sensitisation, nocioceptive inputs are modulated centrally and can lead to an enhancement of pain output in the absence of tissue pathology [36,37].
Altered central processing of pain may be present in patients presenting with long-standing PFP [38–40]. Patients have also been shown to often have excessively negative thoughts towards pain and function. They believe the pain will not get better, and that movement will cause further tissue damage and worsening of the pain [41,42]. Pain catastrophising is thought to influence the shaping and physiological responses to pain, and as such, contributes to the development and maintenance of central sensitisation .
Local tissue pathology models of pain do not fully recognise the role and importance of the central nervous system in the development of pain and disability. It is understood that nocioception is neither sufficient nor necessary for pain , and therefore, a new approach may be needed for patients suffering from long term PFP.
Rationale for a different approach:
High levels of central sensitisation may be present in a subgroup of patients with long-standing PFP [38–40]. Other MSK conditions also present with signs of central sensitisation , for example, low back pain  and shoulder pain . Exercise therapy based upon painful movements has been shown to be beneficial for both low back pain [47,48] and shoulder pain in patients presenting with central sensitisation [49–51]. Littlewood et al. (2013) hypothesised that the response to the painful loaded exercise programme for shoulder pain could be attributed to the therapeutic impact upon the central nervous system. Specifically, the exercise prescribed is aimed at addressing fear avoidance and catastrophising beliefs within a framework of ‘hurt not equalling harm’, and pain described as ‘de-conditioned’ tissue. This having a positive impact on the central nervous system with a modified pain output.
Within the field of PFP, only one study has looked specifically at the effect of high-dose, high-repetition exercise therapy versus low-dose, low-repetition exercise therapy for PFP . Forty-two patients with PFP were randomly assigned into two groups of exercise intervention. Both groups received the same exercise regime 3 x a week for 12 weeks (stationary bike, step-ups, knee extension, squats and step-downs), but one group had high dosage, high repetition; and the other low dosage and low repetition. The high dose group exercised for 1 hour and the low dose for 20 minutes. Pain was allowed during the high dose exercise, but increases in pain were not. The results showed a significant benefit of the high dose exercises versus low dose in terms of pain and function at 12 weeks. The between-group difference was even greater at one year post-intervention, as the high dose group continued to improve in terms of pain and function, while the low dose group had relapsed . This finding is confirmed by a more recent study looking at pain-free exercises and education versus education alone . Compliance diaries completed by the patients indicated that those who performed the exercises with a greater dose had the greater benefit, thus indicating that there exists a similar dose-response to exercise intervention for PFP patients as for other MSK conditions.
 Vahasarja V. Prevalence of chronic knee pain in children and adolescents in northern Finland. Acta Paediatr 1995;84:803–5.
 Molgaard C, Rathleff MS, Simonsen O. Patellofemoral pain syndrome and its association with hip, ankle, and foot function in 16- to 18-year-old high school students: a single-blind case-control study. J Am Podiatr Med Assoc 2011;101:215–22. doi:101/3/215 [pii].
 Osteras B, Osteras HH, Torstensen TA, Vasseljen O, Østerås B, Østerås H, et al. Dose-response effects of medical exercise therapy in patients with patellofemoral pain syndrome: a randomised controlled clinical trial. Physiotherapy 2013;99:126–31. doi:10.1016/j.physio.2012.05.009.
 Thomeé R, Thomee R. A comprehensive treatment approach for patellofemoral pain syndrome in young women. Phys Ther 1997;77:1690–703.
 Fredericson M, Powers CM. Practical management of patellofemoral pain. Clin J Sport Med 2002;12:36–8.
 Cutbill JW, Ladly KO, Bray RC, Thorne P, Verhoef M. Anterior knee pain: a review. Clin J Sport Med 1997;7:40–5.
 Nissen CW, Cullen MC, Hewett TE, Noyes FR. Physical and arthroscopic examination techniques of the patellofemoral joint. J Orthop Sports Phys Ther 1998;28:277–85. doi:10.2519/jospt.19220.127.116.117.
 Powers CM. Rehabilitation of patellofemoral joint disorders: a critical review. J Orthop Sports Phys Ther 1998;28:345–54. doi:10.2519/jospt.1918.104.22.1685.
 Collins NJ, Bierma-Zeinstra SMA, Crossley KM, van Linschoten RL, Vicenzino B, van Middelkoop M, et al. Prognostic factors for patellofemoral pain: a multicentre observational analysis. Br J Sports Med 2013;47:227–33. doi:10.1136/bjsports-2012-091696.
 Rankin G, Rushton A, Olver P, Moore A. Chartered Society of Physiotherapy’s identification of national research priorities for physiotherapy using a modified Delphi technique. Physiother (United Kingdom) 2012;98:260–72.
 Powers CM. Patellofemoral Pain: Proximal, Distal, and Local Factors, 2nd International Research Retreat. J Orthop Sports Phys Ther 2012. doi:10.2519/jospt.2012.0301.
 Selfe J, Callaghan M, Witvrouw E, Richards J, Dey MP, Sutton C, et al. Targeted interventions for patellofemoral pain syndrome (TIPPS): classification of clinical subgroups. BMJ Open 2013;3:e003795. doi:10.1136/bmjopen-2013-003795.
 Doménech J, Sanchis-Alfonso V, Espejo BBB, Domenech J, Sanchis-Alfonso V, Espejo BBB. Changes in catastrophizing and kinesiophobia are predictive of changes in disability and pain after treatment in patients with anterior knee pain. Knee Surg Sports Traumatol Arthrosc 2014;22:2295–300. doi:10.1007/s00167-014-2968-7.
 Clijsen R, Fuchs J, Taeymans J. Effectiveness of exercise therapy in treatment of patients with patellofemoral pain syndrome: systematic review and meta-analysis. Phys Ther 2014;94:1697–708. doi:10.2522/ptj.20130310.
 Van Tiggelen D, Cowan S, Coorevits P, Duvigneaud N, Witvrouw E, D VT, et al. Delayed vastus medialis obliquus to vastus lateralis onset timing contributes to the development of patellofemoral pain in previously healthy men: a prospective study. Am J Sports Med 2009;37:1099–105. doi:10.1177/0363546508331135.
 Luhmann SJ, Schoenecker PL, Dobbs MB, Eric Gordon J. Adolescent patellofemoral pain: implicating the medial patellofemoral ligament as the main pain generator. J Child Orthop 2008;2:269–77. doi:10.1007/s11832-008-0104-2.
 Sheehan FT, Derasari A, Fine KM, Brindle TJ, Alter KE. Q-angle and J-sign: indicative of maltracking subgroups in patellofemoral pain. Clin Orthop Relat Res 2010;468:266–75. doi:10.1007/s11999-009-0880-0.
 Salsich GB, Long-Rossi F. Do females with patellofemoral pain have abnormal hip and knee kinematics during gait? Physiother Theory Pract 2010;26:150–9. doi:10.3109/09593980903423111.
 Dolak KL, Silkman C, Medina McKeon J, Hosey RG, Lattermann C, Uhl TL. Hip strengthening prior to functional exercises reduces pain sooner than quadriceps strengthening in females with patellofemoral pain syndrome: a randomized clinical trial. J Orthop Sports Phys Ther 2011;41:560–70. doi:10.2519/jospt.2011.3499.
 Wilson T. The measurement of patellar alignment in patellofemoral pain syndrome: are we confusing assumptions with evidence? J Orthop Sports Phys Ther 2007;37:330–41.
 Barton C, Balachandar V, Lack S, Morrissey D. Patellar taping for patellofemoral pain: a systematic review and meta-analysis to evaluate clinical outcomes and biomechanical mechanisms. Br J Sports Med 2014;48:417–24. doi:10.1136/bjsports-2013-092437.
 Nakagawa TH, Serrão F V, Maciel CD, Powers CM. Hip and knee kinematics are associated with pain and self-reported functional status in males and females with patellofemoral pain. Int J Sports Med 2013;34:997–1002. doi:10.1055/s-0033-1334966.
 Rathleff MS, Rathleff CR, Crossley KM, Barton CJ. Is hip strength a risk factor for patellofemoral pain? A systematic review and meta-analysis. Br J Sports Med 2014;48:1088. doi:10.1136/bjsports-2013-093305.
 Barton CJ, Lack S, Hemmings S, Tufail S, Morrissey D. The “Best Practice Guide to Conservative Management of Patellofemoral Pain”: incorporating level 1 evidence with expert clinical reasoning. Br J Sports Med 2015;49:923–34. doi:10.1136/bjsports-2014-093637.
 Hossain M, Alexander P, Burls A, Jobanputra P. Foot orthoses for patellofemoral pain in adults. Cochrane Database Syst Rev 2011:CD008402. doi:10.1002/14651858.CD008402.pub2.
 Callaghan MJ, Selfe J. Patellar taping for patellofemoral pain syndrome in adults. Cochrane Database Syst Rev 2012;4:CD006717. doi:10.1002/14651858.CD006717.pub2.
 Smith TO, Hunt NJ, Donell ST. The reliability and validity of the Q-angle: A systematic review. Knee Surgery, Sport Traumatol Arthrosc 2008;16:1068–79.
 Smith TO, Davies L, Donell ST. The reliability and validity of assessing medio-lateral patellar position: a systematic review. Man Ther 2009;14:355–62. doi:10.1016/j.math.2008.08.001.
 Crossley K, Cowan SM, Bennell KL, McConnell J. Patellar taping: is clinical success supported by scientific evidence? Man Ther 2000;5:142–50. doi:10.1054/math.2000.0354.
 Callaghan MJ, Selfe J, Bagley PJ, Oldham JA. The Effects of Patellar Taping on Knee Joint Proprioception. J Athl Train 2002;37:19–24.
 Peters JSJ, Tyson NL. Proximal exercises are effective in treating patellofemoral pain syndrome: a systematic review. Int J Sports Phys Ther 2013;8:689–700.
 Papadopoulos K, Stasinopoulos D, Ganchev D. A Systematic Review of Reviews in Patellofemoral Pain Syndrome . Exploring the Risk Factors , Diagnostic Tests , Outcome Measurements and Exercise Treatment. Open Sport Med J 2015;9:7–17.
 Lankhorst NE, Bierma-Zeinstra SMA, Van Middelkoop M. Risk Factors for Patellofemoral Pain Syndrome: A Systematic Review. J Orthop Sport Phys Ther 2012;42:81–94. doi:10.2519/jospt.2012.3803.
 Sanchis-Alfonso V. Holistic approach to understanding anterior knee pain. Clinical implications. Knee Surg Sports Traumatol Arthrosc 2014. doi:10.1007/s00167-014-3011-8.
 Moseley GL. Reconceptualising pain according to modern pain science. Phys Ther Rev 2007;12:169–78. doi:10.1179/108331907X223010.
 Woolf CJ. Central sensitization: Implications for the diagnosis and treatment of pain. Pain 2011;152.
 Merskey H, Bogduk N. IASP Task Force on Taxonomy Part III: Pain Terms, A Current List with Definitions and Notes on Usage. IASP Task Force Taxon 1994:209–14.
 Jensen R, Kvale A, Baerheim A. Is pain in patellofemoral pain syndrome neuropathic? Clin J Pain 2008;24:384–94. doi:10.1097/AJP.0b013e3181658170.
 Jensen R, Hystad T, Kvale A, Baerheim A. Quantitative sensory testing of patients with long lasting Patellofemoral pain syndrome. Eur J Pain 2007;11:665–76. doi:10.1016/j.ejpain.2006.10.007.
 Rathleff MS, Roos EM, Olesen JL, Rasmussen S, Arendt-Nielsen L. Lower mechanical pressure pain thresholds in female adolescents with patellofemoral pain syndrome. J Orthop Sports Phys Ther 2013;43:414–21. doi:10.2519/jospt.2013.4383.
 Doménech J, Sanchis-Alfonso V, López L, Espejo BB, Domenech J, Sanchis-Alfonso V, et al. Influence of kinesiophobia and catastrophizing on pain and disability in anterior knee pain patients. Knee Surgery, Sport Traumatol Arthrosc 2013;21:1562–8. doi:10.1007/s00167-012-2238-5.
 Piva SR, Fitzgerald GK, Irrgang JJ, Fritz JM, Wisniewski S, McGinty GT, et al. Associates of physical function and pain in patients with patellofemoral pain syndrome. Arch Phys Med Rehabil 2009;90:285–95. doi:10.1016/j.apmr.2008.08.214.
 Quartana PJ, Campbell CM, Edwards RR. Pain catastrophizing: a critical review. Expert Rev Neurother 2009;9:745–58. doi:10.1586/ern.09.34.
 Nijs J, Van Houdenhove B, Oostendorp RAB. Recognition of central sensitization in patients with musculoskeletal pain: Application of pain neurophysiology in manual therapy practice. Man Ther 2010;15:135–41.
 Giesecke T, Gracely RH, Grant MAB, Nachemson A, Petzke F, Williams DA, et al. Evidence of Augmented Central Pain Processing in Idiopathic Chronic Low Back Pain. Arthritis Rheum 2004;50:613–23.
 Littlewood C, Malliaras P, Bateman M, Stace R, May S, Walters S. The central nervous system – An additional consideration in “rotator cuff tendinopathy” and a potential basis for understanding response to loaded therapeutic exercise. Man Ther 2013;18:468–72. doi:10.1016/j.math.2013.07.005.
 Long A, Donelson R, Fung T. Does it matter which exercise? A randomized control trial of exercise for low back pain. Spine (Phila Pa 1976) 2004;29:2593–602.
 Cook C, Hegedus EJ, Ramey K. Physical Therapy Exercise Intervention Based on Classification Using the Patient Response Method: A Systematic Review of the Literature. J Man Manip Ther 2005;13:152–62. doi:10.1179/106698105790824950.
 Littlewood C, Malliaras P, Mawson S, May S, Walters SJ. Self-managed loaded exercise versus usual physiotherapy treatment for rotator cuff tendinopathy: A pilot randomised controlled trial. Physiother (United Kingdom) 2014;100:54–60. doi:10.1016/j.physio.2013.06.001.
 Bernhardsson S, Klintberg IH, Wendt GK. Evaluation of an exercise concept focusing on eccentric strength training of the rotator cuff for patients with subacromial impingement syndrome. Clin Rehabil 2011;25:69–78. doi:10.1177/0269215510376005.
 Holmgren T, Bjornsson Hallgren H, Oberg B, Adolfsson L, Johansson K, Björnsson Hallgren H, et al. Effect of specific exercise strategy on need for surgery in patients with subacromial impingement syndrome: randomised controlled study. BMJ 2012;344:e787. doi:10.1136/bmj.e787.
 Osteras B, Osteras H, Torstensen TA, Torsensen TA, Osterås B, Osterås H, et al. Long-term effects of medical exercise therapy in patients with patellofemoral pain syndrome: results from a single-blinded randomized controlled trial with 12 months follow-up. Physiotherapy 2013;99:311–6. doi:10.1016/j.physio.2013.04.001.
 Rathleff MS, Roos EM, Olesen JL, Rasmussen S. Exercise during school hours when added to patient education improves outcome for 2 years in adolescent patellofemoral pain: a cluster randomised trial. Br J Sports Med 2015;49:406–12. doi:10.1136/bjsports-2014-093929.