PainRelief.com: What should readers take away from your report?
Response: The results from our study show that both high-dose and low-dose exercise therapy is beneficial for knee osteoarthritis. At a glance, it would be natural to think that I should choose a low-dose because it takes only 30 minutes and consists of 5 different exercises compared to the high-dose lasting 70 to 90 minutes consisting of 11 exercises. But because our study was designed as a superiority trial, meaning that even though we failed to show that high-dose treatment is superior to low-dose, our results do not imply that a low-dose exercise regimen is as beneficial as a high-dose regimen.
Both groups improved over time, but there were no benefits of high-dose therapy in most comparisons. One exception was the KOOS score function in sports and recreation, where high-dose therapy was superior at the end of treatment and the 6-month follow-up. A small benefit in QoL at 6 months was also observed. Notably, most variables numerically favored the high-dose group, albeit not in a statistically or clinically meaningful way.
In conclusion, the results from our study show that you can use both low- and high-dose effectively. Clinically, what exercise dose you choose depends probably more on how the patient is presenting him/herself. If you have a person who is very motivated to exercise, and the goal of the treatment is to return to sports/recreational-related activities one should aim for a higher exercise dose. For another person, who is not used to exercise, but wants a decrease in symptoms maintaining good function, a low-dose should be tried first with a higher dose as an alternative. It is obvious and common sense that it is easier to adhere to an exercise program that takes 30 minutes to perform compared to 70-90 minutes, which is also supported by our data (1).
In our study, we measured the outcome after every two weeks during the 12-week intervention period a total of six measurement points. And there is really no difference between the groups during the intervention period. One explanation could be that it takes six to 12 treatments to reach the exercise dose described in the study as high-dose while the low-dose treatment could easily be performed after two to three treatments. Another factor is that the interaction between the treating physiotherapist and the patient create positive psychological reactions. This placebo mechanism could have hampered the physiological effects of exercise dose (2,3) in relation to the the painmodulating systems. After the end of treatment, where these placebo effects are not present any longer, there are some differences between groups in favor of high-dose exercise. Another factor that may have influenced the outcome is the 20% lower compliance to the exercises in the high-dose group compared to the low-dose group implying a nocebo mechanism. All in all, it is easier to perform five exercises taking 30 minutes.
Strengths of the study:
-A superiority trial
-Multinational multicenter RCT
-The exercise interventions high-dose and low-dose are based on the principles from medical exercise therapy which is an established form of exercise therapy.
-The physiotherapists treating the patients had long clinical experience using these methods.
-High compliance for both high-dose and low-dose
-No reports of adverse or serious adverse effects
-Multiple measurement points (n=6, every second week) during the 12 week treatment period.
-Long term follow-up, six and 12 months after end of treatment
-Valid and reliable outcome measures
-Robust statistical methods, high resolution with repeated measures during the intervention, and 2 longterm follow-ups
-Published in a high impact international journal
Limitations of the study
-Multiple measurements during the intervention period creating a possible recall bias
-Ceiling effects for KOOS
-Floor effects for VAS
-Missing data both during the intervention period and at 6- and 12 months follow-ups
-Higher drop-outs for high-dose (n=12) compared to low-dose (n=4) during the intervention period
-20% lower adherence in the high-dose group compared to low-dose regarding exercise dose
-The different limitations can have influenced the power of the study
PainRelief.com: Is there anything else you would like to add? Any disclosures?
Response: A useful tip to practitioners is to have a closer look at the theoretical description of medical exercise therapy (MET) which of course applies equally to both low-dose and high-dose (4-7). The primary goal using MET is to grade and dose the exercises so that they are performed pain-free or close to pain-free using the principles of self-pacing (7). As a clinician, you want to create a positive atmosphere when the patient is exercising and avoiding nocebo (8). The interaction between the physiotherapist and the patient makes it also possible to observe the patient’s behavior in relation to a possible endurance behavior (9). This interaction makes it also possible to apply a form of cognitive behavioral therapy using principles from the field of psychology like graded exposure and acceptance.
Research has shown that compliance is higher when exercises are performed pain-free (10) and comfortably (11,12) not causing anxiety. Finally, we also argue (1,4) that it is not possible to perform strength training when you have pain because the experience of pain decreases motor output making it only possible to do strength training when you are symptom-free (13), and that to intensive exercise therapy can also cause adverse effects like an increase in pain decreasing motivation (14). To break the vicious circle of long-term knee pain, we believe it is important to see beyond the knee, beyond an impairment such as muscle strength, using a biopsychosocial sensitization model of pain (4).
- Torstensen TA, Østerås H, LoMartire R, Rugelbak GM, Grooten WJA, Äng BO. High-verus Low-Dose Exercise Therapy for Knee Osteoarthritis: A Randomized Controlled Multicenter Trial. Ann Intern Med 2023 Jan 24.doi: 10.7326/M22-2348
- Craig AD. A new view of pain as a homeostatic emotion. Trends Neurosci 2003;26:303–7.
- Ingvar M. Learning mechanisms in pain chronification – teachings from placebo research. Pain 2015;156:S18–S23
“The seminal article of Craig with the description of pain as a homoeostatic emotion moved the field away from the concept of a “searching for pain center” in the brain to a systems-oriented understanding. The experience of pain was put in a behavioural perspective and the dynamics of the preprogrammed complex emotional reactions to acute pain were explained in terms of a dynamic regulatory system. Just as in all other expressions of emotion, the homoeostasis model for understanding pain provides both a basis for a prolongation of the feeling state but also, at the same time, an effective measure of social communication to alert others of, eg, danger. In addition, such a mechanism also serves to raise empathic responses in the group. The understanding of pain as a homoeostatic emotion has also contributed to the understanding of affective comorbidity in different pain syndromes because the mechanisms of both lowered mood and anxiety are based on similar regulatory mechanisms. However, the mentioned mechanisms are mostly represented in the phylogenetically old components of the central nervous system. The role of the cerebral cortical regulation in chronic pain remains a challenge to fully explain”, Ingvar M (2015) pp:S18, line 13-31.
Ingvars review presents a general model for the understanding of pain, placebo, and chronification of pain in the framework of cognitive neuroscience. Both Craig and Ingvars views are helpful understanding the importance of expectations (positive expectations = placebo, negative expectations = nocebo) and the social environment where these expectations are created, either decreasing the feeling of pain due to placebo or increasing the feeling of pain due to nocebo. In our publication (1) references 39-42 are on the subject of placebo nocebo and that the effects from placebo nocebo can explain why we have not been able to show that high dose is superior to low dose. Unfortunately, we do not have a third group getting no treatment, which is a weakness of the study. On the other hand, our study should be looked at as a “niche” type of RCT where the hypothesis was that high dose was better than low dose (A superiority trial) and that we never intended to have a control group getting no treatment.
- Torstensen TA, Grooten WJA, Østerås H, et al. How does exercise dose affect patients with long-term osteoarthritis of the knee? A study protocol of a randomised controlled trial in Sweden and Norway: the SWENOR Study. BMJ Open 2018;8:e018471. doi:10.1136/bmjopen-2017-018471
- Lorås H, Østerås B, Torstensen TA, et al. Medical Exercise Therapy for Treating Musculoskeletal Pain: A Narrative Review of Results from Randomized Controlled Trials with a Theoretical Perspective. Physiother Res Int 2015;20:182-90.
- Torstensen TA. A software programmer and sportsman with low back pain and sciatica. In: Jones MA and Rivett DA, editors. Clinical Reasoning for Manual Therapists. New York: Butterworth Heineman; 2004, p:275-311.
- Williams DM. Exercise, affect, and adherence: an integrated model and a case for self-paced exercise. J Sport Exerc Psychol 2008;30:471–96.
- Colloca L, Benedetti F. Nocebo hyperalgesia: how anxiety is turned into pain. Curr Opin Anaesthesiol. 2007;20:435–9.
Fabrizio Benedetti and his research group in Turin, Italy have made great contributions to our understaning of the importance of the context of clinical practice and the interrelationship between a health professional and the patient, placebo- and nocebo mechanisms. Their research showing how anxiety (nocebo) is turned into pain (8) is a real game changer and fits well with the theories of Bud Craig (2) and Martin Ingvar (3). Benedettis research fits also very well with Ekkekakis P views (11 and 12) that compliance to exercise therapy is closely linked to how a person emotionally expierences the exercise. This again fits well with the theoretical basis for medical exercise therapy (4-6) including both high and low dose (1,4), grading and dosing exercises so that they are performe pain-free or close to pain-free not causing any anxiety using the principle of self-pacing (7).
- Hasenbring MI, Chehadi O, Titze C, et al. Fear and anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance. Pain Manag 2014;4:363–74.
- Dipnarine K, Barak S, Martinez CA, et al. Pain-free treadmill exercise for patients with intermittent claudication: Are there gender differences? Vascular 2016;24:304–14.
- Ekkekakis P. People have feelings! Exercise psychology in paradigmatic transition. Curr Opin Psychol 2017;16:84–8.
- Brand R, Ekkekakis P. Affective–Reflective Theory of physical inactivity and exercise. Foundations and preliminary evidence. Ger J Exerc Sport Res 2018 · 48:48–58
References 6 to 12 above support the view that it is important to dose and grade exercise pain-free or close to pain-free which is the case for both high- and low dose MET.
- Henriksen M, Rosager S, Aaboe J, et al. Experimental knee pain reduces muscle strength. J Pain 2011;12:460–7.
- Liu CJ, Latham N. Adverse events reported in progressive resistance strength training trials in older adults: 2 sides of a coin. Arch Phys Med Rehabil 2010;91:1471–3.
There is today evidence that pain itself inhibits motor output and that we should stop using the concept of strength training when a patient is suffering from pain. It can instead cause adverse effects like an increase in symptoms and decrease a persons motivation to exercise (14). Instead we should use exercise as a form of cognitive behavioral therapy breaking the vicious circle of long-term knee pain. Thus, it is important to see beyond the knee, beyond an impairment such as muscle strength, using a biopsychosocial sensitization model of pain (4). This applies to both high- and low dose MET.
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