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The disconnect between tissue pathology, load and pain: implications for clinicians



The 2024 Global Year will examine what is known about sex and gender differences in pain perception and modulation and address sex-and gender-related disparities in both the research and treatment of pain.

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For at least two decades, we have known that for chronic pain conditions there is discrepancy between tissue damage seen on clinical imaging and clinical presentation. You can have a severely osteoarthritic X-ray with no pain, or a completely normal X-ray with severe pain. Despite this disparity, imaging findings, such as meniscal tears, rotator cuff tears and degenerative discs are often interpreted as causes of pain, triggering medical and surgical interventions. But given the disconnect with actual symptoms, it is perhaps not surprising that interventions to remove/fix the tissue or targeting tissue regeneration, such as arthroscopy, stem cells or platelet rich plasma, are often no more effective in reducing symptoms than sham treatments [1].

In light of growing concern of overdiagnosis, our recent systematic review and meta-analysis of 63 studies of 5,397 completely asymptomatic uninjured knees revealed that knee osteoarthritis features assessed on MRI (cartilage defects, meniscal tears and osteophytes) were common (up to 60% in those aged >60 years) [2]. Their prevalence, instead of being associated with pain, was closely linked to age. A majority of these features, when assessed clinically, should be viewed like wrinkles on the skin – a normal part of aging that don’t typically require ‘fixing’.

One might theorise the reverse relationship, that even if osteoarthritis presence doesn’t predict pain, pain presence might predict progression of osteoarthritis. Surprisingly, that theory was also refuted in our recent longitudinal study that followed up patients with imaging 15 and 20 years post-anterior cruciate ligament reconstruction [3]. Neither the presence, nor persistence, of patellofemoral pain in the years post-operatively predicted any significant difference in patellofemoral osteoarthritis 15-20 years later.

Pain and related disability are normally the primary concern for patients seeking treatment. The persistence of pain experience in response to mechanical stimuli is often thought to indicate adverse tissue loads from a biological perspective, leading to interventions aimed at tissue ‘offloading’ to prevent injury or degeneration. Counterintuitively, offloading tissues in the context of musculoskeletal pain may be more problematic than beneficial for tissue health. For example, following acute knee injury, which places young adults at high risk of early-onset knee osteoarthritis, those who actually developed osteoarthritis walked with lower peak knee contact forces (2.10 x body weight) than those who didn’t develop osteoarthritis (2.89 x body weight) [4].

Furthermore, one-third of adolescents who develop patellofemoral pain are sedentary [5]. In addition to the potential for mechanotherapy (ie. promotion of tissue repair/remodelling with exercise-therapy) [6], tissue loading through exercise can also have acute sensory effects – improving pain by reducing a sensitised nervous system through a reduction in cortical inhibition [7]. It is important to remember that clinical changes occur beyond the resolution of imaging and/or tissue mechanical properties.

Pain can persist with safe tissue loads. Even when persistent pain displays ‘mechanical’ behaviour, this could represent the early or unnecessary warnings from a sensitised nervous system, as much or more than any threat to tissues. For example, patellofemoral pain, often considered mechanical in origin with greater pain in activities that apply greater load to the knee, is characterised by local and widespread hyperalgesia indicating a combination of peripheral and central mechanisms driving pain [8]. Approaches to pain management therefore need to consider more than just mechanical effects of altering tissue load, because positive adaptations knock-on to affect other domains. Exercises with gradual progression of loads, intended for mechanotherapy can also be viewed as neurosensory-therapy (modulating sensitisation and motor control) as well behavioural therapy (modulating thoughts and feelings related to body use).

Pain should not typically be a barrier for tissue and joint loading, but it is an important clinical consideration when planning how much load will provoke a sensitised nervous system. For example, for patients with chronic knee and hip pain, a program of progressive loading (strengthening) resulted in sensory adaptations leading to a considerable decrease in exercise-induced pain flares [9]. Even in acute injury settings, where traditional first-line injury management was rest (the R in RICE), guidelines have now shifted and advocate ‘protect and optimally load’ (the POL in POLICE) [10].

There is need for vigilance but not fear of gradual progressive loading interventions for people with persistent musculoskeletal pain. The potential acute benefits for the sensory nervous system, the long-term benefits on tissue mechanical properties and minimising degeneration, as well as the general health benefits are all valuable. Even in the presence of persistent musculoskeletal pain, gradual progression of tissue loading through exercise is likely to be more friend than foe.

About Adam Culvenor

Adam is a physiotherapist and NHMRC Early Career Research Fellow at La Trobe University Sport and Exercise Medicine Research Centre, Melbourne. His research focusses on the genesis and progression of musculoskeletal pain and osteoarthritis over the lifespan, its impact on individuals and society, and effective non-surgical interventions. His research has been awarded American Journal of Sports Medicine best paper 2016, Australian Physiotherapy Association Best New Investigator in musculoskeletal research 2013, and has been recognised by the European Research Council (career development prize 2017). E-mail: a.culvenor@latrobe.edu.au

Andrew Claus

Andrew lectures in physiotherapy at The University of Queensland. A focus of his teaching in the undergraduate and postgraduate programmes is the topic of pain. Andrew advises: “This BiM post centres around Adam’s outstanding recent publications. My contribution was some questions and ideas. The example of persistent anterior knee pain failing to predict significant OA over 15-20 yrs, forces us to question past assumptions that persistent ‘mechanical’ pain is driven by persistent mechanical injury.”


[1] Thorlund JB, Juhl CB, Roos EM, Lohmander LS: Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. BMJ 2015, 350:h2747.

[2] Culvenor AG, Oiestad BE, Hart H, Stefanik JJ, Guermazi A, Crossley KM: Prevalence of knee osteoarthritis features on magnetic resonance imaging in asymptomatic uninjured adults: a systematic review and metaanalysis. British Journal of Sports Medicine 2018, epub ahead of print.

[3] Culvenor AG, Oiestad BE, Holm I, Gunderson R, Crossley KM, Risberg MA: Anterior knee pain following anterior cruciate ligament reconstruction does not increase the risk of patellofemoral osteoarthritis at 15- and 20-year follow-ups. Osteoarthritis & Cartilage 2017, 25:30-33.

[4] Wellsandt E, Gardinier ES, Manal K, Axe MJ, Buchanan TS, Snyder-Mackler L: Decreased knee joint loading associated with early knee osteoarthritis after anterior cruciate ligament injury. American Journal of Sports Medicine 2016, 44:143-151.

[5] Rathleff MS, Vicenzino B, Van Middelkoop M, Graven-Nielsen T, Van Linschoten R, Holmich P, Thorborg K: Patellofemoral pain in adolescence and adulthood: same same, but different? Sports Medicine 2015, 45:1489-1495.

[6] Khan KM, Scott A: Mechanotherapy: how physical therapists’ prescription of exercise promotes tissue repair. British Journal of Sports Medicine 2009, 43:247-251.

[7] Rio E, Kidgell D, Purdam C, Gaida J, Moseley GL, Pearce AJ, Cook K: Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy. British Journal of Sports Medicine 2015, 49:1277-1283.

[8] Rathleff MS, Roos EM, Olesen JL, Rasmussen S, Arendt-Nielsen L: Lower mechanical pressure pain thresholds in female adolescents with patellofemoral pain syndrome. Journal of Orthopaedic & Sports Physical Therapy 2013, 43:414-421.

[9] Sandal LF, Roos EM, Bogesvang SJ, Thorlund JB: Pain trajectory and exercise-induced pain flares during 8 weeks of neuromuscular exercise in individuals with knee and hip pain. Osteoarthritis & Cartilage 2016, 24:589-592.

[10] Bleakley CM, Glasgow P, MacAuley DC: PRICE needs updating, should we call the POLICE? 2012, 46:220-221.

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