Pain inhibition and post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study


Van Oosterwijck J, Nijs J, Meeus M, Lefever I, Huybrechts L, Lambrecht L, Paul L


Department of Human Physiology, Faculty of Physical Education and Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium


To examine the efficacy of the pain inhibitory systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) during two different types of exercise and to examine whether the (mal)functioning of pain inhibitory systems is associated with symptom increases following exercise.


A controlled experimental study.

Setting and Subjects

Twenty-two women with ME/CFS and 22 healthy sedentary controls were studied at the Department of Human Physiology, Vrije Universiteit Brussel.


All subjects performed a submaximal exercise test and a self-paced, physiologically limited exercise test on a cycle ergometer. The exercise tests were undertaken with continuous cardiorespiratory monitoring. Before and after the exercise bouts, subjects filled out questionnaires to assess health status, and underwent pressure pain threshold measurements. Throughout the study, subjects’ activity levels were assessed using accelerometry.


In patients with ME/CFS, pain thresholds decreased following both types of exercise, whereas they increased in healthy subjects. This was accompanied by a worsening of the ME/CFS symptom complex post-exercise. Decreased pressure thresholds during submaximal exercise were associated with postexertional fatigue in the ME/CFS group (r=0.454; P=0.034).


These observations indicate the presence of abnormal central pain processing during exercise in patients with ME/CFS and demonstrate that both submaximal exercise and self-paced, physiologically limited exercise trigger postexertional malaise in these patients. Further study is required to identify specific modes and intensity of exercise that can be performed in people with ME/CFS without exacerbating symptoms.


Journal of Internal Medicine, 2010 Sep; 268(3): 265–78

Comment by ME Research UK

Despite the concerns of patient support groups and charities, the National Institute for Clinical Excellence (NICE) Clinical Guideline currently recommends “cognitive-behavioural” therapies, including graded exercise therapy (GET), for people with ME/CFS. The guideline does, however, make clear that it does not regard these interventions as “curative or directed at the underlying disease process, which remains unknown. Rather, such interventions can help some patients cope with the condition and experience improved functioning, and consequently an improved quality of life.” (NICE Guideline, full version, page 252).

And the results of the largest clinical trial to date (the PACE trial) have confirmed this view, showing that while cognitive behavioural therapies can modestly improve outcomes compared with standard medical care, they are far from being the panacea that is sometimes claimed.

Yet the reality is that in the consulting room or at the clinic, people with ME/CFS are “prescribed” GET for their condition, and some even report being pressurised into undertaking formal exercise programmes. This is particularly worrying because patient surveys suggest that GET might be harmful in some patients; for instance, the 2002 Chief Medical Officer’s report quoted a survey in which 50% of 1,214 patients said they had been “made worse” by GET, while in a 2010 survey 33.1% of 906 patients reported that it had made them “much worse”.

It is important to understand why many patients experience a worsening of symptoms after exercise, particularly 24 to 48 hours later. While a range of pathophysiological mechanisms could be involved, one possible element might be a disruption to the pain inhibitory system in ME/CFS. This system normally controls the release of analgesic (pain-relieving) chemicals and other factors during exercise, which cause an increase in pain thresholds; put simply, if this system is working properly we do not feel pain so readily when we exercise. There is evidence that this threshold decreases during and after exercise in ME/CFS patients, suggesting that the pain inhibitory system may be impaired.

The objective of this study was to determine whether a worsening in symptoms after exercise in ME/CFS patients is indeed related to dysfunction of the pain inhibitory system. The investigators used a device called an algometer (or algorimeter) to measure pain thresholds before and after exercise in 22 women with ME/CFS as well as 22 healthy women matched for age and body mass index. An algometer consists of a pressure gauge attached to a narrow rod, the end of which is pushed against the subject’s skin until he or she reports feeling pain. The pressure at which this occurs can be read from the gauge and indicates the pain pressure threshold. This was measured between the thumb and forefinger on both hands, at both calves, and on the back.

Algometry was performed before and after two different types of exercise test on a cycle ergometer. In the first test, subjects cycled continuously at about 60 to 70 revolutions per minute while the resistance (and hence the workload) was increased until the subject’s heart rate reached 75% of the predicted maximum, or until they were unable to continue. This was the “submaximal” exercise test.

In the second test (conducted a week later), subjects were asked to estimate how long they thought they could cycle before their symptoms got worse, and they then cycled for a period that was 50 to 75% shorter than their estimate. In addition, heart rate and workload limits were chosen to keep the exercise intensity well below the subject’s anaerobic threshold (i.e. the point at which lactic acid starts to accumulate in the muscles). This was the “self-paced” and physiologically limited exercise test.

The participants also filled in questionnaires to assess the severity of their symptoms, their functional status and wellbeing, and the severity of their fatigue.

The differences between ME/CFS patients and healthy subjects were clear. In the patients, pain pressure thresholds decreased by up to 10% at most measurement sites following both types of exercise, meaning individuals were more sensitive to pain after exercise than they were before. In the healthy subjects the opposite was true: their pain pressure thresholds consistently increased after exercise by an average of 10%, meaning they had become less sensitive to pain.

Furthermore, ME/CFS patients also experienced a worsening of their symptoms after exercise; pain was dramatically higher in the patients than in the control subjects, increasing even further 24 hours after both types of exercise. Levels of fatigue were also increased, and directly correlated with the drop in pain thresholds in the patients.

The researchers conclude that these results suggest the pain inhibitory system is indeed impaired in ME/CFS, because it did not respond to exercise in the patient group as it did in the control group. And also that this dysfunction may be at least partially responsible for the increase in symptoms that patients regularly experience after exercise (a number of other mechanisms may also potentially be involved).

Given that self-paced exercise is to be preferred routinely to the rigours of a full-blown exercise programme, an accompanying expert editorial in the same issue of the Journal of Internal Medicine suggests that “the time may have come to replace the concept of ‘graded exercise therapy’ with ‘paced exercise therapy’ in CFS, using flexible and individually tailored exercise programmes that not only augment patients’ physical condition but also help them to better recognize ‘bodily signals’ and connect these to realistic goals and aspirations.

This essay is an extract from our article (pdf 1 MB) in the Spring 2011 issue of Breakthrough.

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