Jo Nijs

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Jo Nijs, PT, MT, PhD,[1] is a Belgian professor of physiotherapy at the Vrije Universiteit Brussel and physiotherapist/manual therapist at the University Hospital Brussels. He is Scientific Chair of the executive committee of the Pain, Mind and Movement Special Interest Group of the International Association for the Study of Pain (IASP)[2] and holder of the Chair 'Exercise immunology and chronic fatigue in health and disease' funded by the European College for Decongestive Lymphatic Therapy.[3] Nijs plays a leading role in the Pain in Motion research group,[4] an international collaborative that studies the interplay between chronic pain and movement. While he advocates graded exercise as a treatment for ME/CFS, he argues that it should be preceded by a stabilization phase in which patients pace themselves to find the right balance between rest and activity.[5] Nijs is mostly known for espousing the theory of central sensitization[6]: he suspects ME/CFS to be a dysfunction of the central nervous system,[7][8] characterized by a heightened sensitivity to pain and other stimuli such as light, sounds and chemical substances.[9]

Background[edit | edit source]

Under the guidance of De Meirleir: a biomedical approach[edit | edit source]

After graduating in rehabilitations sciences, Nijs started working as a physiotherapist in private practice where he came into contact with ME/CFS patients. He was intruiged by their condition and decided to do a PhD about it.[10] At the Vrije Universiteit Brussel (VUB) Nijs started working under the guidance of Dr. Kenny De Meirleir, who is known for his biomedical approach to the illness.[11] In the mid-2000s De Meirleir and Nijs published a number of studies together regarding the infectious and immunologic aspects of ME/CFS, including mycoplasma infection[12] and defects in the 2.5A Synthetase RNase L antiviral pathway.[13]

Tracking the activities of ME/CFS-patients [edit | edit source]

The Chronic fatigue syndrome activities and participation questionnaire (CFS-APQ)[edit | edit source]

In his PhD, Nijs took on the task of devising a new activities questionnaire for ME/CFS. Many of the surveys that were used at the time such as the Short Form 36-Item Health Survey (SF-36), Karnofsky scores and the Symptom Checklist (SCL-90) were not specific to this illness, so they might overlook important aspects of ME/CFS-disability. By analyzing various questionnaires retrospectively,[14] Nijs came up with 26 new questions that map out the particular limitations ME/CFS-patients face (e.g. making the bed, preparing meals, reading etc.). The questionnaire, called the 'Chronic Fatigue Syndrome Activities and Participation Questionnaire' (CFS-APQ), showed good construct validity and internal consistency[15] but was unable to differentiate between ME/CFS and fibromyalgia patients.[16]

Daily physical activity in ME/CFS[edit | edit source]

Nijs has researched how a reliable measurement of the daily activities of ME/CFS patients could be obtained. He has agued that the 'International Physical activity questionnaire-short form' (IPAQ-sf) might be inappropriate since it focused mostly on strenuous efforts and vigorous activities, which are hardly performed by ME/CFS patients.[17] As an alternative, Nijs proposes to use more direct measures such as an accelerometer that tracks step counts and an activity diary. In a 2011 study, Nijs used these techniques to follow up on the activities of 67 ME/CFS patients and 66 healthy controls.[18] Patients were significantly less active compared to sedentary controls. The study was however unable to confirm the fluctuating activity pattern of ME/CFS patients; they did not concentrate their activities more in peaks, as was suggested by Leonard Jason.[19] Nijs’ study showed a correlation between time spent being more active on the one hand and pain, fatigue and concentration difficulties on the other hand. According to the authors "this can be interpreted as more physical activity resulting in more complaints and more fluctuations in the fatigue." A 2013 study by Nijs' research group showed that there was no significant correlation between activity levels and cognitive performance in 31 ME/CFS patients.[20] Another study suggested increased physical activity to have beneficial effects on sleep quality in ME/CFS.[21]

The value of exercise testing in ME/CFS[edit | edit source]

Nijs has worked on the issue of exercise testing in ME/CFS. Because of post-exertional malaise, it is not always possible for ME/CFS-patients to reach their VO2 Max. Based on the exercise testing of more than 200 ME/CFS-patients, Nijs demonstrated (in succession to Mullis et al.[22]) that other values such as peak workload or VO2 submax can be used to correctly predict VO2 Max.[23][24]

In a review of exercise testing in ME/CFS, Nijs concluded that despite some conflicting studies, “the weighted available evidence points towards a reduced physiological exercise capacity in CFS".[8] The authors concluded that a lack of uniformity in diagnostic criteria, could explain for the differences between studies. Yet, while ME/CFS patients showed a reduced physiological exercise capacity, there was only a minor correlation between exercise test results and employment rate, suggesting this might not be a reliable measure to assess disability.[25]

Exercise therapy[edit | edit source]

Exercise limits[edit | edit source]

Nijs tested the use of exercise limits as a method to prevent post-exertional setbacks in ME/CFS patients.[26] In a 2008 study, patients had to estimate the amount of exercise (walking) they could handle without triggering post-exertional malaise. Because it was assumed patients would overestimate their capacities, this amount was reduced by 25% if the person was having a good day and 50% if she was having a bad day. Another exercise limit involved a maximal heart rate (the heart rate that corresponded with a respiratory exchange ratio of 1 on an exercise test), that patients could not exceed during walking. Despite these precautions, patients still experienced a worsening of their symptoms after exertion. Because this relapse was short-lived, Nijs concluded that the exercise limits had worked and prevented important health status changes.

Two years later the Nijs’ research group conducted a similar study. Twenty-two ME/CFS test-subjects had to perform a submaximal exercise test and a paced cycling regime. Patients could only do 75% (on a good day) or 50% (on a bad day) of what they thought they could handle without triggering a relapse, while a maximal heart rate was set at 80% of their anaerobe threshold. Once again, despite these precautions, patients experienced a worsening of their condition after both pacing and the submaximal exercise test, a deterioration that was not seen in healthy controls.[27]

A symptom-contingent exercise program[edit | edit source]

In 2008, Nijs collaborated with Karen Wallman and Lorna Paul to work out an exercise program for ME/CFS that took into account post-exertional malaise. Although it was still instructed to exercise progressively and to build up stamina, the key advice was that patients should listen to their body while doing so. They could for example change their schedule if they were having a bad day. Nijs et al. criticized earlier approaches that used a time-contingent approach where patients have to follow a pre-set plan, regardless of how they were feeling. 

"Early approaches to graded exercise therapy advised patients to continue exercising at the same level when they developed symptoms in response to the exercise. This led to exacerbation of symptoms and adverse feedback from patients and patient charities."[28]

To prevent relapses, Nijs, Paul and Wallman advised to build in a long stabilization phase in which patients had to find the right balance between rest and activity. With this approach, symptom fluctuation has to be reduced to a manageable level first. Only when the patient feels that she can cope with a certain level, can it be decided to build up exercises. This form of self-management combined with graded exercise was criticized by Lucy Clark and Peter White. They emphasized that a graded exercise program has to be time-contingent to be effective: 

"[…] a central concept of GET is that patients maintain their level of exercise as much as possible even after a CFS/ME setback. This is to reduce the many negative consequences of rest and allow the body to habituate to the increase in activity."[29]

In 2011, Nijs & Wallman collaborated with Leonard Jason, who had helped develop the Energy Envelope Theory, and Ellen Goudsmit, who had studied the use of pacing. Together they worked out a 'consensus document' about the main principles of the pacing in ME/CFS. According to the authors there was a "lack of information on the efficacy of time-contingent protocols in people with evidence of neurological or immunological disease."[30] Nijs and colleagues proposed an approach where patients limited their activities in response to internal cues of post-exertional malaise. Patients were only advised to gently increase their activity levels if their health had stabilized and they were close to about 60 to 70% of their former functioning.

A U-turn towards time contingent-exercise [edit | edit source]

In 2012 (after the first results of the controverial PACE-trial were published) the research group of Nijs made a U-turn and started advocating a time-contingent form of graded exercise.[31] This position was criticized by Tom Kindlon[32] who pointed out that studies supporting graded exercise therapy were almost solely based on subjective measures. Nijs et al. responded: 

"We agree with Tom Kindlon that such evidence is based on self-report rather than on objective measures, but in the end of the day, patients prefer treatments that make them feel better (subjectively) over treatments that improve objective blood results (but at the same time leave them feeling sick)."[33]

Regarding the argument that numerous patients surveys had shown that GET can have detrimental effects on the health of ME/CFS patients, Nijs et al. replied: 

"Such surveys have value, but from a scientific viewpoint, it remains an unanswered question who filled out these surveys (nothing but patients with ME/CFS diagnosed by a physician?), to what extent selection bias, suggestion and recall bias have contributed to the study findings, etc. One cannot exclude the possibility that the survey results reflect the difficulty of clinicians around the globe to apply exercise therapy for patients with ME/CFS."[33]

Activity pacing self-management (APSM)[edit | edit source]

According to Nijs, the PACE-authors made a mistake by placing GET in opposition to pacing. He argues the two can and should be used together, in what he calls 'Activity Pacing Self-Management' (APSM). In a first phase, pacing is used to stabilize the health condition of the patient and let her know that exercise doesn't always have to result in a relapse. Only when this is achieved (and this can take several weeks) is it advised to move on to a second, graded phase where a progressive time-contingent approach is used. According to APSM, activities should only be increased incrementally according to a personalized, pre-set schedule. Sufficient rest periods are included after each activity to prevent serious relapses.   

Nijs tested his APSM approach in a 2015 randomized controlled trial in which the control group received relaxation therapy. The results were favorable, though no objective performance measures were used. The study was also rather small as only 16 ME/CFS patients were involved in the experimental APSM group, of which 4 (25%) stopped the treatment prematurely.[5]

Kinesiophobia and catastrophizing: testing the fear-avoidance model [edit | edit source]

Nijs has investigated the fear avoidance model in ME/CFS. In this model, originally developed for chronic low back pain, it is believed patients worsen their condition by holding an irrational fear of movement called kinesiophobia. When Nijs tested this in 64 ME/CFS patients, the results contradicted the theory:

"Our data do not support the view that kinesiophobia is associated with disability (ie, activity limitations and participation restrictions) in patients with CFS who experience pain. Our results, therefore bring into question the clinical importance of kinesiophobia."[34]

Two other studies by Nijs, both published in 2004, did find a relationship between kinesiophobia and activity limitations measured with the CFS-APQ, but there was no correlation with exercise test results.[35]

Another concept of the fear avoidance model is catastrophizing, a tendency to interpret events negatively or to assume the worst will happen. In a group of 36 ME/CFS patients, Nijs found that “catastrophizing accounted for 41% of the variance in bodily pain."[36] These results were questioned by Tom Kindlon who pointed out the study could not prove the assumed direction of causation. The lack of correlation between catastrophizing and the large drop in employment rate seen in the ME/CFS patients studied, suggests other factors might be more important in determining their condition."[37]

In 2011, Nijs collaborated with Gijs Bleijenberg to test the effect of kinesiophobia and catastrophizing in ME/CFS before a threatening activity, in this case, stair climbing. Both factors were unrelated to symptom expectancies, but they did correlate with actual stair climbing performance, i.e. the time required to complete the task.[38] Two years later the study was repeated using a larger sample of 49 ME/CFS patients. Findings contradicted those of the previous study as kinesiophobia and catastrophizing were no longer related to stair climbing duration.[39]

In 2012, Nijs' research group concluded that catastrophizing is a long-term predictor of pain in ME/CFS patients.[40] In a 2013 review Nijs concluded that fear of movement was a highly prevalent and a clinically relevant factor in ME/CFS.[41]

Unravelling the nature of post-exertional malaise[edit | edit source]

Searching for a PEM-biomarker[edit | edit source]

In several studies, the Nijs research group investigated the nature of post-exertional malaise, often with funding of ME research UK (MERUK).[42] One of their studies looked at immune factors after exercise and found a relationship between the change in complement C4a split product levels and the increase in pain and fatigue. According the authors this suggested C4a has the potential to become a biomarker for post-exertional malaise in ME/CFS.[27] In two other studies the Pain in Motion research group showed that heart rates of ME/CFS patients recovered more slowly after exercise compared to controls.[43][44] A 2018 study looked at cerebral blood flow and heart rate variability after exercise, but did not reveal meaningful results.[45]

With or without fibromyalgia[edit | edit source]

In 2014, Nijs researched the recovery of muscle in function and its relationship to cognitive performance in ME/CFS. The most important finding was the difference between patients with and without comorbid fibromyalgia. In the former group, recovery of upper limb muscle function was found to be slower[46] and a significant predictor of cognitive performance.[47] In a study comparing various ME/CFS criteria using objective measures,[48] Nijs and colleagues found that neither the old ME-criteria, nor the Canadian Consensus Criteria selected patients were worse off than those who fulfilled the Fukuda criteria. Only the subgroup with comorbid fibromyalgia scored significantly worse on objective tests, as the recovery of their muscles was slower than in ME/CFS patients without FM.

Central sensitization[edit | edit source]

Chronic pain might be more disabling than chronic fatigue[edit | edit source]

Most of Jo Nijs’ research focuses on the treatment of chronic pain. He argues that fatigue has been arbitrarily put forward as the primary symptom of ME/CFS patients.[49] In his own research, he found that pain explained as much of the activity limitations and participation restrictions of ME/CFS patients as fatigue,[50] concluding that chronic pain might thus be more disabling than chronic fatigue in this disease.[51]

An increased reactivity of the central nervous system[edit | edit source]

Nijs suspects pain in ME/CFS might be explained be the process of 'central sensitization' (CS). This refers to a heightened responsiveness of the central nervous system (CNS) to nociceptive stimuli. Because no lesions or neural damage can be found to explain the pain of ME/CFS patients, it is assumed that the CNS overreacts to normal stimuli, seeing them as more threatening than they are. According to Nijs this might explain why ME/CFS patients often perceive painful stimuli as more intense (hyperalgesia) or experience pain after normally innocuous stimuli (allodynia). Nijs has argues that CS might also explain other symptoms besides pain, such as the sensitivity to light, sound and various chemicals that many ME/CFS patients display.[9]

Secondary hyperalgesia[edit | edit source]

Researchers use various methods to evaluate if the CNS overreacts to stimuli. The easiest way is to measure pain thresholds all over the body, using an algometer. The research team of Nijs tested this in 30 ME/CFS patients who were suffering from chronic pain. Pain pressure thresholds were significantly lower compared to those of the control group when pain-free areas of the body were tested (a phenomenon known as secondary hyperalgesia).[52] In an additional study it was shown that ME/CFS patients experienced more pain following heat stimuli.[53]

Wind-up and temporal summation[edit | edit source]

Another method to test CS is to look at ‘temporal summation’, also called wind up. This refers to the process where neurons of the CNS respond to a repeated stimuli with an increased reactivity. If one quickly repeats a fixed noxious stimulus 10 times, then the last one will be experienced as more painful that the first. Researchers can measure the amount of ‘wind up’ of the neurons by looking at the difference between the first and the last stimulus. In chronic pain conditions like fibromyalgia, that difference is greater than in normal controls, suggesting these patients experience a heightened form of temporal summation. Nijs’ research group tested this procedure in 48 ME/CFS patients, but the results were ambiguous. There was only a difference in windup compared to control subjects if the pain stimuli were administered to the finger and not to the shoulder.[54]

Conditioned pain modulation: pain inhibits pain[edit | edit source]

Central sensitization doesn’t necessary involve an increased susceptibility to stimuli. It can also be explained by a defect in the inhibitory pain pathways of the body. One highly researched mechanism in this respect is called 'conditioned pain modulation' or CPM (an older name is 'diffuse noxious inhibitory control'). This refers to the fact that pain in one area of the body can decrease pain in another area. Nijs’ research group tested this in 2009 using heat stimuli showing that conditioned pain modulation was normal but delayed in ME/CFS patients.[53] In two other studies,[55][54] Nijs' research group tested CPM using the pressure of an inflatable occlusion cuff as the conditioning stimulus. In both cases there were no differences between ME/CFS patients and healthy controls.

Endogenous pain inhibition after exercise [edit | edit source]

Another way to induce endogenous inhibition is to exercise. When healthy people exercise, their brain induces the production of endorphins that increase pain thresholds. In some chronic pain patients like fibromyalgia and whiplash associated disorders, this endogenous pain inhibition is defective and pain thresholds decrease shortly after exercise (i.e. they experience more pain while they should be feeling less). In 2004, Whiteside et al.[56] first showed this defect in ME/CFS patients, though their study only involved five patients. The Pain in Motion group of Nijs and colleagues confirmed these results in two of their studies.[57][58] While pain thresholds increased in normal controls, they decreased in the ME/CFS patient group. These studies however, only included ME/CFS that were suffering from chronic pain.[9] It therefore remains uncertain whether similar results will also show up in ME/CFS patients that do not have comorbid FM.[59]

Criteria for the classification of central sensitization pain[edit | edit source]

Jo Nijs is regarded as an international expert in central sensitization. He has researched CS in patients with chronic spinal pain, chronic low back pain,[60] shoulder pain,[61] knee osteoarthritis,[62] cancer-related pain[63] and chronic whiplash.[64] In 2014, he was first author of a consensus paper in which 18 experts set out criteria for the diagnosis of central sensitivity.[65] After neuropathic pain has been ruled out, the criteria propose to assess if the severity of pain is “disproportionate to the nature and extent of injury and pathology”. This is an obligatory criterion; if pain is not disproportionate, then it doesn’t involve CS. Secondly it is proposed to look at the pain distribution; if pain is widespread and diffuse then the clinician can diagnose CS in his patient. If this is not the case, then the clinician can use the central sensitization inventory (CSI), a questionnaire that has been developed to assess CS and mostly looks at secondary symptoms like sensitivity to light, bad sleep and concentration problems. If the patient scores 40 or more on the CSI, than the clinician can make the diagnosis of CS.  

Treating central sensitization[edit | edit source]

Together with long-time collaborator Mira Meeus, Nijs wrote two reviews[66][67] on the treatment of CS. Special attention goes to medications that target central pathways of the pain response. One example is acetaminophen (paracetamol) that reinforces the inhibitory serotonergic pathway. Meeus & Nijs tested this in ME/CFS patients with comorbid fibromyalgia. Though pain thresholds rose, there was no influence on temporal summation or conditioned pain modulation.[55]

Selective serotonin reuptake inhibitors (SSRIs) also activate the serotonergic descending pathways. In a 2011 study, Meeus & Nijs gave their test subjects intravenous SSRI (citalopram) but the trial had to be stopped prematurely, since the medication caused too many side-effects.[68]

Opioids form another option, although these drugs are now restricted and rather controversial because they can lead to addiction[69] and cause selective pain sensitization. In 2017 Meeus & Nijs tested morphine and naloxone (an opioid antagonist) against a placebo, but the results were rather bleak: 

"[...] neither morphine nor naloxone influenced deep tissue pain, temporal summation or CPM. Therefore, these results suggest that the opioid system is not dominant in (enhanced) bottom-up sensitization (temporal summation) or (impaired) endogenous pain inhibition (CPM) in patients with CFS/FM or RA."[70]

There are other therapeutic options to treat central sensitization like N-methyl-D-aspartate –receptor antagonists (e.g. ketamine), GABA-antagonists  (e.g. pregabalin) or a ketogenic diet. Nijs & Meeus also propose exercise therapy and emphasize that a time-contingent approach is preferable in treating CS:

"A symptom-contingent approach may facilitate the brain in its production of nonspecific warning signs like pain, whereas a time-contingent approach may deactivate brain-orchestrated top-down pain facilitatory pathways."[67]

The authors do however caution that this approach might not work in every CS-patient group: 

"[...] some patients with CS pain, including those with chronic whiplash associated disorders , chronic fatigue syndrome and fibromyalgia, are unable to activate endogenous analgesia following exercise. It remains to be established whether long-term exercise therapy accounting for the dysfunctional endogenous analgesia is able to 'treat' CS in these patients."[67]

Controversy[edit | edit source]

Pain neurophysiology education[edit | edit source]

Before starting exercise therapy in CS patients, Nijs promotes the use of ‘pain neurophysiology education’, in which the patient is told that pain doesn’t always involve nociceptive input and vice versa. Nijs emphasized that this method might convince patients wary of a psychological approach:

"The innovative aspect of pain physiology education is the use of physiology (i.e., the mechanism of central sensitization) to change perceptions and cognitions. This makes it appropriate even for CFS cases reluctant to the biopsychosocial model."[71]

Tom Kindlon questioned ‘neurophysiology education’ since it advises to ignore chronic pain while little is known about the mechanisms and etiology of pain in ME/CFS. Kindlon also criticized one of the primary justifications for the pain management program; that it might increase therapy adherence - that is adherence to graded exercise therapy:

“Until a particular exercise regimen has been shown to be safe in CFS, in the interim it seems questionable, and indeed possibly unethical, to have adherence to such an intervention as the goal of any educational program.”[72]

Is it unethical to question GET? [edit | edit source]

In 2013, Nijs' position towards GET was questioned by Twisk & Arnoldus. Nijs reposted that it was 'unethical' to downplay the effectiveness of GET for ME/CFS patients:

"[…] at the group level, there is no doubt that graded exercise therapy and cognitive behavioural therapy are effective treatments for ME/CFS. Saying the reverse might prevent clinicians from applying these treatments to their ME/CFS patients. In the absence of alternative treatment options (recall that besides graded exercise therapy and cognitive behavioural therapy, no other treatment has proven to be beneficial to ME/CFS patients), this would be unethical."[73]

Nijs also suggested that opposition to GET might be fuelled by a conflict of interest of patient advocates: 

"At the same time, one can imagine that refuting the evidence favouring conservative interventions for ME/CFS might be inspired by a conflict of interest (e.g. personal interest in biopharmaceutical companies or as a ME/CFS patient running for a disability payment)."[73]

Are ME/CFS and fibromyalgia the same? [edit | edit source]

The publications of Nijs and collagues often lump ME/CFS and fibromyalgia together as if they are one disorder. For example in their 2013 book on the treatment of persistent fatigue directed at clinicians (written in Dutch),[74] no distinction is made between ME/CFS and fibromyalgia. The rationale behind this is that both disorders have similar symptoms and are (supposedly) characterized by central sensitization. Most researchers however emphasize the importance of dealing with ME/CFS and fibromyalgia separately, since there might be biological differences between the two.[75]

Notable studies[edit | edit source]

  • 2002, High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients[12] - (Full Text)
  • 2002, Activity Limitations and Participation Restrictions in Patients with Chronic Fatigue Syndrome—Construction of a Disease Specific Questionnaire[14] - (Abstract)
  • 2003, Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome[76] - (Abstract)
  • 2003, Deregulation of the 2,5A Synthetase RNase L Antiviral Pathway by Mycoplasma spp. in Subsets of Chronic Fatigue Syndrome[13] - (Full Text)
  • 2003, Comparison of Activity Limitations/Participation Restrictions Among Fibromyalgia and Chronic Fatigue Syndrome Patients[16] - (Abstract)
  • 2003, Immunophenotyping Predictive of Mycoplasma Infection in Patients with Chronic Fatigue Syndrome?[77] - (Abstract)
  • 2003, Monitoring a Hypothetical Channelopathy in Chronic Fatigue Syndrome: Preliminary Observations[78] - (Abstract)
  • 2004, Lack of Association Between Pain-Related Fear of Movement and Exercise Capacity and Disability[34] - (Full text)
  • 2004, Kinesiophobia in chronic fatigue syndrome: assessment and associations with disability[35] - (Full text)
  • 2004, Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome[23] - (Abstract)
  • 2004, Review - Gulf War Veterans: Evidence for Chromosome Alterations and Their Significance[79] (Abstract)
  • 2004, Construct validity and internal consistency of the chronic fatigue syndrome activities and participation questionnaire (CFS-APQ)[15] - (Abstract)
  • 2005, Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation?[49] - (Full text)
  • 2005, Employment status in chronic fatigue syndrome. A cross-sectional study examining the value of exercise testing and self-reported measures for the assessment of employment status[25] - (Abstract)
  • 2007, Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: a systematic review[51] - (Abstract)
  • 2007, Can submaximal exercise variables predict peak exercise performance in women with chronic fatigue syndrome?[24] - (Abstract)
  • 2007, Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome[6] - (Full text)
  • 2008, Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study[53] - (Abstract)
  • 2008, Response to letter to the editor by Lucy V. Clark And PeterD. White. Prevention of symptom exacerbations in chronic fatigue syndrome[29] - (Letter, Full text)
  • 2008, Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations[28] - (Abstract)
  • 2008, Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial[26] - (Full text)
  • 2010, Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study[57] - (Abstract)
  • 2010, Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study[52] - (Abstract)
  • 2010, Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study[58] - (Full text)
  • 2010, Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1beta.[27] - (Full text)
  • 2011, Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?[66] - (Full text)
  • 2011, Symptom fluctuations and daily physical activity in patients with chronic fatigue syndrome: a case-control study[18] - (Full text)
  • 2011, Serotonergic descending inhibition in chronic pain: design, preliminary results and early cessation of a randomized controlled trial[68] - (Full text)
  • 2011, Is the International Physical Activity Questionnaire-short form (IPAQ-SF) valid for assessing physical activity in Chronic Fatigue Syndrome?[17] - (Full text)
  • 2011, Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome[8] - (Abstract)
  • 2012, Pain in patients with chronic fatigue syndrome: time for specific pain treatment?[71] - (Abstract)
  • 2012, Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study[40] - (Abstract)
  • 2012, Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study[38] - (Abstract)
  • 2012, How to exercise people with chronic fatigue syndrome: evidence-based practice guidelines[31] - (Full text)
  • 2012, In the mind or in the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome[9] - (Full text)
  • 2012, Ignoring the evidence favouring exercise therapy for chronic fatigue syndrome is unethical and scientifically incorrect[73] - (Full text)
  • 2012, Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document[30] - (Full text)
  • 2013, Fear of movement and avoidance behaviour toward physical activity in chronic-fatigue syndrome and fibromyalgia: state of the art and implications for clinical practice[41] - (Abstract)
  • 2013, Influence of symptom expectancies on stair-climbing performance in chronic fatigue syndrome: effect of study context[39] - (Abstract)
  • 2013, Association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome[20] - (Full text)
  • 2013, Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning[7] - (Abstract)
  • 2013, Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial[55] - (Abstract)
  • 2013, The role of mitochondrial dysfunctionsq due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?[80] - (Abstract)
  • 2014, Can recovery of peripheral muscle function predict cognitive task performance in chronic fatigue syndrome with and without fibromyalgia?[47] - (Abstract)
  • 2014, Recovery of upper limb muscle function in chronic fatigue syndrome with and without fibromyalgia[46] - (Abstract)
  • 2014, Treatment of central sensitization in patients with 'unexplained' chronic pain: an update[67] - (Abstract)
  • 2014, Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review[81] (Full Text)
  • 2015, Reduced parasympathetic reactivation during recovery from exercise in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)[43] - (Full text)
  • 2015, Activity Pacing Self-Management in Chronic Fatigue Syndrome: A Randomized Controlled Trial[5] - (Full text)
  • 2016, What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia[48] - (Abstract)
  • 2016, Editorial Comment - Rehabilitation for patients with myalgic encephalomyelitis/chronic fatigue syndrome: time to extent the boundaries of this field[82] (Full Text)
  • 2017, Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study[70] - (Abstract)
  • 2017, Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study[54] - (Full Text)
  • 2017, The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People[44] (Full Text)
  • 2018, Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A Randomized Cross-Over Study[45] - (Full text)
  • 2018, Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing[36] - (Full text)
  • 2018, Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - a secondary analysis of experimental comparative studies[83] - (Full text)
  • 2019, Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects[84] - (Full text)
  • 2019, Treatment of central sensitization in patients with chronic pain: time for change?[85] - (Full text)
  • 2020, DNA Methylation and Brain‐Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia[86] - (Full text)
  • 2021, Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome[87] - (Full text)
  • 2021, Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine[88] - (Full text)
2021, Central sensitisation: causes, therapies, and terminology – Authors' reply[89] - (Letter, Full text)

Talks and interviews[edit | edit source]

Online presence[edit | edit source]

Learn more[edit | edit source]

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References[edit | edit source]

  1. ↑ "Jo Nijs". Researchgate. Retrieved April 2, 2022.
  2. ↑ "Nijs, Jo". World Conference on Physical Therapy. 2017. Archived from the original on April 2, 2017. Retrieved April 2, 2022.
  3. ↑ "Chair de Berekuyl". Vrije Universiteit Brussel (in Nederlands). Retrieved April 2, 2022.
  4. ↑ "Members". Pain in Motion (in Nederlands). Retrieved April 2, 2022.
  5. ↑ 5.0 5.1 5.2 Nijs, Jo; Paul, Lorna; Wallman, Karen (April 2008). "Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations". Journal of Rehabilitation Medicine. 40 (4): 241–247. doi:10.2340/16501977-0185. ISSN 1650-1977. PMID 18382818.
  6. ↑ 6.0 6.1 Meeus, Mira; Nijs, Jo (April 2007). "Central sensitization: a biopsychosocial explanation for chronic widespread pain in patients with fibromyalgia and chronic fatigue syndrome". Clinical Rheumatology. 26 (4): 465–473. doi:10.1007/s10067-006-0433-9. ISSN 0770-3198. PMC 1820749. PMID 17115100.
  7. ↑ 7.0 7.1 Nijs, J.; Ickmans, K. (February 8, 2013). "Postural orthostatic tachycardia syndrome as a clinically important subgroup of chronic fatigue syndrome: further evidence for central nervous system dysfunctioning". Journal of Internal Medicine. 273 (5): 498–500. doi:10.1111/joim.12034. ISSN 0954-6820.
  8. ↑ 8.0 8.1 8.2 Nijs, Jo; Aelbrecht, Senne; Meeus, Mira; Van Oosterwijck, Jessica; Zinzen, Evert; Clarys, Peter (2001). "Tired of being inactive: a systematic literature review of physical activity, physiological exercise capacity and muscle strength in patients with chronic fatigue syndrome" (PDF). Disability and Rehabilitation. 33 (17–18): 1493–1500. doi:10.3109/09638288.2010.541543. ISSN 1464-5165. PMID 21166613.
  9. ↑ 9.0 9.1 9.2 9.3 Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Ickmans, Kelly; Moorkens, Greta; Hans, Guy; De Clerck, Luc S. (February 2012). "In the mind or in the brain? Scientific evidence for central sensitisation in chronic fatigue syndrome: CENTRAL SENSITISATION IN CFS". European Journal of Clinical Investigation. 42 (2): 203–212. doi:10.1111/j.1365-2362.2011.02575.x.
  10. ↑ "ME/CVS Stichting. Interview met Prof. Dr. Jo Nijs" (PDF). Pain in Motion.
  11. ↑ Englebienne, Patrick; Meirleir, Kenny De (February 27, 2002). Chronic Fatigue Syndrome: A Biological Approach. CRC Press. ISBN 978-1-4200-4100-2.
  12. ↑ 12.0 12.1 Nijs, Jo; De Meirleir, Kenny L.; Coomans, Danny; De Becker, Pascale; Nicolson, Garth L. (2002). "High prevalence of Mycoplasma infections among European chronic fatigue syndrome patients. Examination of four Mycoplasma species in blood of chronic fatigue syndrome patients". FEMS Immunology and Medical Microbiology. 34 (3): 209-14. doi:10.1111/j.1574-695X.2002.tb00626.x. PMID 12423773.
  13. ↑ 13.0 13.1 Nijs, Jo; De Meirleir, Kenny L.; Coomans, Danny; De Becker, Pascale; Nicolson, Garth L. (2003). "Deregulation of the 2,5A Synthetase RNase L Antiviral Pathway by Mycoplasma spp. in Subsets of Chronic Fatigue Syndrome" (PDF). Journal of Chronic Fatigue Syndrome. 11 (2): 37-50. doi:10.1300/J092v11n02_04.
  14. ↑ 14.0 14.1 Nijs, Jo; Vaes, Peter; Van Hoof, Elke; De Becker, Pascale; McGregor, Neil; De Meirleir, Kenny L. (2002). "Activity Limitations and Participation Restrictions in Patients with Chronic Fatigue Syndrome—Construction of a Disease Specific Questionnaire". Journal of Chronic Fatigue Syndrome. 10 (2): 3-23. doi:10.1300/J092v10n03_02.
  15. ↑ 15.0 15.1 Nijs, Jo; Cloostermans, Benedicte; McGregor, Neil; Vaes, Peter; DeMeirleir, Kenny (January 1, 2004). "Construct validity and internal consistency of the chronic fatigue syndrome activities and participation questionnaire (CFS-APQ)". Physiotherapy Theory and Practice. 20 (1): 31–40. doi:10.1080/ptp.20.1.31.40. ISSN 0959-3985.
  16. ↑ 16.0 16.1 Nijs, Jo; Vaes, Peter; McGregor, Neil; Lambrecht, Luc; Van Hoof, Elke; De Meirleir, Kenny L. (2003). "Comparison of Activity Limitations/Participation Restrictions Among Fibromyalgia and Chronic Fatigue Syndrome Patients". Journal of Chronic Fatigue Syndrome. 11 (4). doi:10.1300/J092v11n04_02.
  17. ↑ 17.0 17.1 Meeus, Mira; Van Eupen, Inge; Willems, Joke; Kos, Daphne; Nijs, Jo (2011). "Is the International Physical Activity Questionnaire-short form (IPAQ-SF) valid for assessing physical activity in Chronic Fatigue Syndrome?". Disability and Rehabilitation. 33 (1): 9–16. doi:10.3109/09638288.2010.483307. ISSN 1464-5165. PMID 20446802.
  18. ↑ 18.0 18.1 Meeus, Mira; Eupen, Inge van; Baarle, Ellen van; Boeck, Valérie De; Luyckx, Anke; Kos, Daphne; Nijs, Jo (November 1, 2011). "Symptom Fluctuations and Daily Physical Activity in Patients With Chronic Fatigue Syndrome: A Case-Control Study". Archives of Physical Medicine and Rehabilitation. 92 (11): 1820–1826. doi:10.1016/j.apmr.2011.06.023. ISSN 0003-9993.
  19. ↑ Jason, L.A.; King, C.P.; Frankenberry, E.L.; Jordan, K.M.; Tryon, W.W.; Rademaker, F.; Huang, C.F. (April 1999). "Chronic fatigue syndrome: assessing symptoms and activity level". Journal of Clinical Psychology. 55 (4): 411–424. ISSN 0021-9762. PMID 10348404.
  20. ↑ 20.0 20.1 Ickmans, Kelly; Clarys, Peter; Nijs, Jo; Meeus, Mira; Aerenhouts, Dirk; Zinzen, Evert; Aelbrecht, Senne; Meersdom, Geert; Lambrecht, Luc; Pattyn, Nathalie (2013). "Association between cognitive performance, physical fitness, and physical activity level in women with chronic fatigue syndrome" (PDF). Journal of Rehabilitation Research and Development. 50 (6): 795–810. doi:10.1682/JRRD.2012.08.0156. ISSN 1938-1352. PMID 24203542.
  21. ↑ Aerenhouts, Dirk; Ickmans, Kelly; Clarys, Peter; Zinzen, Evert; Meersdom, Geert; Lambrecht, Luc; Nijs, Jo (2015). "Sleep characteristics, exercise capacity and physical activity in patients with chronic fatigue syndrome". Disability and Rehabilitation. 37 (22): 2044–2050. doi:10.3109/09638288.2014.993093. ISSN 1464-5165. PMID 25512240.
  22. ↑ Mullis, R.; Campbell, I.T.; Wearden, A.J.; Morriss, R.K.; Pearson, D.J. (October 1, 1999). "Prediction of peak oxygen uptake in chronic fatigue syndrome". British Journal of Sports Medicine. 33 (5): 352–356. doi:10.1136/bjsm.33.5.352. ISSN 0306-3674. PMID 10522640.
  23. ↑ 23.0 23.1 Nijs, Jo; De Meirleir, Kenny (November 2004). "Prediction of peak oxygen uptake in patients fulfilling the 1994 CDC criteria for chronic fatigue syndrome". Clinical Rehabilitation. 18 (7): 785–792. doi:10.1191/0269215504cr751oa. ISSN 0269-2155.
  24. ↑ 24.0 24.1 Nijs, Jo; Demol, Seppe; Wallman, Karen (April 1, 2007). "Can Submaximal Exercise Variables Predict Peak Exercise Performance in Women with Chronic Fatigue Syndrome?". Archives of Medical Research. 38 (3): 350–353. doi:10.1016/j.arcmed.2006.10.009. ISSN 0188-4409.
  25. ↑ 25.0 25.1 Nijs, Jo; Van de Putte, Karen; Louckx, Fred; De Meirleir, Kenny (December 2005). "Employment status in chronic fatigue syndrome. A cross-sectional study examining the value of exercise testing and self-reported measures for the assessment of employment status". Clinical Rehabilitation. 19 (8): 895–899. doi:10.1191/0269215505cr882oa. ISSN 0269-2155.
  26. ↑ 26.0 26.1 Nijs, Jo; Almond, Freya; De Becker, Pascale; Truijen, Steven; Paul, Lorna (May 2008). "Can exercise limits prevent post-exertional malaise in chronic fatigue syndrome? An uncontrolled clinical trial". Clinical Rehabilitation. 22 (5): 426–435. doi:10.1177/0269215507084410. ISSN 0269-2155. PMID 18441039.
  27. ↑ 27.0 27.1 27.2 Nijs, J.; Van Oosterwijck, J.; Meeus, M.; Lambrecht, L.; Metzger, K.; Frémont, M.; Paul, L. (2010). "Unravelling the nature of postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: the role of elastase, complement C4a and interleukin-1β". Journal of Internal Medicine. 267 (4): 418–435. doi:10.1111/j.1365-2796.2009.02178.x. ISSN 1365-2796.
  28. ↑ 28.0 28.1 Nijs, Jo; Paul, Lorna; Wallman, Karen (April 2008). "Chronic fatigue syndrome: an approach combining self-management with graded exercise to avoid exacerbations". Journal of Rehabilitation Medicine. 40 (4): 241–247. doi:10.2340/16501977-0185. ISSN 1650-1977. PMID 18382818.
  29. ↑ 29.0 29.1 Nijs, Jo; Paul, Lorna; Wallman, Karen (November 2008). "Chronic fatigue syndrome and Response to Letter to the Editor by Lucy V. Clark and PeterD. White: Prevention of symptom exacerbations in chronic fatigue syndrome". Journal of rehabilitation medicine: official journal of the UEMS European Board of Physical and Rehabilitation Medicine. 40 (10). doi:10.2340/16501977-0261.
  30. ↑ 30.0 30.1 Goudsmit, Ellen; Nijs, Jo; Jason, Leonard A.; Wallman, Karen E. (2012). "Pacing as a strategy to improve energy management in myalgic encephalomyelitis/chronic fatigue syndrome: a consensus document". Disability and Rehabilitation. 34 (13): 1140–7. doi:10.3109/09638288.2011.635746. PMID 22181560.
  31. ↑ 31.0 31.1 Van Cauwenbergh, Deborah; De Kooning, Margot; Ickmans, Kelly; Nijs, Jo (June 23, 2012). "How to exercise people with chronic fatigue syndrome: evidence-based practice guidelines". European Journal of Clinical Investigation. 42 (10): 1136–1144. doi:10.1111/j.1365-2362.2012.02701.x. ISSN 0014-2972.
  32. ↑ Kindlon, Tom (2012). "Objective compliance and outcome measures should be used in trials of exercise interventions for Chronic Fatigue Syndrome". European Journal of Clinical Investigation. 42 (12): 1360–1361. doi:10.1111/j.1365-2362.2012.02724.x. ISSN 1365-2362.
  33. ↑ 33.0 33.1 Nijs, Jo; Van Cauwenbergh, Deborah; De Kooning, Margot; Ickmans, Kelly (September 15, 2012). "Time-contingent pacing and exercise therapy accounting for postexertional malaise and central sensitization in chronic fatigue (central sensitivity) syndrome". European Journal of Clinical Investigation. 42 (12): 1363–1365. doi:10.1111/j.1365-2362.2012.02722.x. ISSN 0014-2972.
  34. ↑ 34.0 34.1 Nijs, Jo; Vanherberghen, Katrien; Duquet, William; De Meirleir, Kenny (August 2004). "Chronic fatigue syndrome: lack of association between pain-related fear of movement and exercise capacity and disability". Physical Therapy. 84 (8): 696–705. ISSN 0031-9023. PMID 15283620.
  35. ↑ 35.0 35.1 Nijs, Jo; Meirleir, Kenny De; Duquet, William (October 1, 2004). "Kinesiophobia in chronic fatigue syndrome: Assessment and associations with disability1". Archives of Physical Medicine and Rehabilitation. 85 (10): 1586–1592. doi:10.1016/j.apmr.2003.12.033. ISSN 0003-9993.
  36. ↑ 36.0 36.1 Nijs, Jo; Van de Putte, Karen; Louckx, Fred; Truijen, Steven; De Meirleir, Kenny (November 2008). "Exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing". Pain Medicine (Malden, Mass.). 9 (8): 1164–1172. doi:10.1111/j.1526-4637.2007.00368.x. ISSN 1526-4637. PMID 19086101.
  37. ↑ Kindlon, T (2009). "Response to: exercise performance and chronic pain in chronic fatigue syndrome: the role of pain catastrophizing". Pain Med. 10 (6): 1144.
  38. ↑ 38.0 38.1 Nijs, Jo; Meeus, Mira; Heins, Marianne; Knoop, Hans; Moorkens, Greta; Bleijenberg, Gijs (2012). "Kinesiophobia, catastrophizing and anticipated symptoms before stair climbing in chronic fatigue syndrome: an experimental study". Disability and Rehabilitation. 34 (15): 1299–1305. doi:10.3109/09638288.2011.641661. ISSN 1464-5165. PMID 22324510.
  39. ↑ 39.0 39.1 Heins, Marianne; Knoop, Hans; Nijs, Jo; Feskens, Remco; Meeus, Mira; Moorkens, Greta; Bleijenberg, Gijs (June 2013). "Influence of symptom expectancies on stair-climbing performance in chronic fatigue syndrome: effect of study context". International Journal of Behavioral Medicine. 20 (2): 213–218. doi:10.1007/s12529-012-9253-2. ISSN 1532-7558. PMID 22865100.
  40. ↑ 40.0 40.1 Meeus, Mira; Nijs, Jo; Van Mol, Evelyne; Truijen, Steven; De Meirleir, Kenny (June 2012). "Role of psychological aspects in both chronic pain and in daily functioning in chronic fatigue syndrome: a prospective longitudinal study". Clinical Rheumatology. 31 (6): 921–929. doi:10.1007/s10067-012-1946-z. ISSN 1434-9949. PMID 22349876.
  41. ↑ 41.0 41.1 Nijs, Jo; Roussel, Nathalie; Van Oosterwijck, Jessica; De Kooning, Margot; Ickmans, Kelly; Struyf, Filip; Meeus, Mira; Lundberg, Mari (August 2013). "Fear of movement and avoidance behaviour toward physical activity in chronic-fatigue syndrome and fibromyalgia: state of the art and implications for clinical practice". Clinical Rheumatology. 32 (8): 1121–1129. doi:10.1007/s10067-013-2277-4. ISSN 1434-9949. PMID 23639990.
  42. ↑ "Pain inhibition and post-exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study". ME Research UK. Retrieved April 3, 2022.
  43. ↑ 43.0 43.1 Oosterwijck, J. Van; Marusic, U.; Wandele, I. De; Meeus, M.; Paul, L.; Lambrecht, L.; Moorkens, G.; Nijs, J. (May 1, 2015). "Reduced parasympathetic reactivation during recovery from exercise in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS)". Physiotherapy. 101: e1091–e1092. doi:10.1016/j.physio.2015.03.1984. ISSN 0031-9406.
  44. ↑ 44.0 44.1 Nijs, J; Danneels, L; Lambrecht, L; Moorkens, G; Meeus, M; Paul, L; Van Oosterwijck, J; Marusic, U; De Wandele, I (2017). "The Role of Autonomic Function in Exercise-induced Endogenous Analgesia: A Case-control Study in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Healthy People". Pain Physician. 20 (3): E389–E399. PMID 28339438.
  45. ↑ 45.0 45.1 Malfliet, A; Pas, R; Brouns, R; De Win, J; Hatem, SM; Meeus, M; Ickmans, K; van Hooff, RJ; Nijs, J (2018). "Cerebral Blood Flow and Heart Rate Variability in Chronic Fatigue Syndrome: A Randomized Cross-Over Study". Pain Physician. 21 (1): E13-E24.
  46. ↑ 46.0 46.1 Ickmans, Kelly; Meeus, Mira; De Kooning, Margot; Lambrecht, Luc; Nijs, Jo (December 9, 2013). "Recovery of upper limb muscle function in chronic fatigue syndrome with and without fibromyalgia". European Journal of Clinical Investigation. 44 (2): 153–159. doi:10.1111/eci.12201. ISSN 0014-2972.
  47. ↑ 47.0 47.1 Ickmans, Kelly; Meeus, Mira; De Kooning, Margot; Lambrecht, Luc; Pattyn, Nathalie; Nijs, Jo (April 2014). "Can recovery of peripheral muscle function predict cognitive task performance in chronic fatigue syndrome with and without fibromyalgia?". Physical Therapy. 94 (4): 511–522. doi:10.2522/ptj.20130367. ISSN 1538-6724. PMID 24363336.
  48. ↑ 48.0 48.1 Meeus, Mira; Ickmans, Kelly; Struyf, Filip; Kos, Daphne; Lambrecht, Luc; Willekens, Barbara; Cras, Patrick; Nijs, Jo (January 2016). "What is in a name? Comparing diagnostic criteria for chronic fatigue syndrome with or without fibromyalgia". Clinical Rheumatology. 35 (1): 191–203. doi:10.1007/s10067-014-2793-x. ISSN 1434-9949. PMID 25308475.
  49. ↑ 49.0 49.1 Nijs, Jo; Van de Velde, Bart; De Meirleir, Kenny (January 1, 2005). "Pain in patients with chronic fatigue syndrome: Does nitric oxide trigger central sensitisation?". Medical Hypotheses. 64 (3): 558–562. doi:10.1016/j.mehy.2004.07.037. ISSN 0306-9877.
  50. ↑ Nijs J, Vaes P, McGregor N, Van Hoof E, De Meirleir K. Psychometric properties of the Dutch chronic fatigue syndrome–activities and participation questionnaire (CFS–APQ). Phys Ther 2003;83:444–54
  51. ↑ 51.0 51.1 Meeus, Mira; Nijs, Jo; Meirleir, Kenny De (May 1, 2007). "Chronic musculoskeletal pain in patients with the chronic fatigue syndrome: A systematic review". European Journal of Pain. 11 (4): 377–386. doi:10.1016/j.ejpain.2006.06.005. ISSN 1090-3801.
  52. ↑ 52.0 52.1 Meeus, Mira; Nijs, Jo; Huybrechts, Sven; Truijen, Steven (April 2010). "Evidence for generalized hyperalgesia in chronic fatigue syndrome: a case control study". Clinical Rheumatology. 29 (4): 393–398. doi:10.1007/s10067-009-1339-0. ISSN 1434-9949. PMID 20077123.
  53. ↑ 53.0 53.1 53.2 Meeus, Mira; Nijs, Jo; Van de Wauwer, Naomi; Toeback, Linda; Truijen, Steven (October 15, 2008). "Diffuse noxious inhibitory control is delayed in chronic fatigue syndrome: an experimental study". Pain. 139 (2): 439–448. doi:10.1016/j.pain.2008.05.018. ISSN 1872-6623. PMID 18617327.
  54. ↑ 54.0 54.1 54.2 Polli, Andrea; Willekens, Barbara; Meeus, Mira; Nijs, Jo; Collin, Simon M.; Ickmans, Kelly (2017). "Endogenous Pain Facilitation Rather Than Inhibition Differs Between People with Chronic Fatigue Syndrome, Multiple Sclerosis, and Controls: An Observational Study Observational Study". Pain Physician. 20 (4): E489-E497. PMID 28535557.
  55. ↑ 55.0 55.1 55.2 Meeus, Mira; Ickmans, Kelly; Struyf, Filip; Hermans, Linda; Van Noesel, Kevin; Oderkerk, Jorinde; Declerck, Luc S.; Moorkens, Greta; Hans, Guy; Grosemans, Sofie; Nijs, Jo (March 2013). "Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? A double-blind randomized controlled cross-over trial". Pain Physician. 16 (2): E61–70. ISSN 2150-1149. PMID 23511692.
  56. ↑ Whiteside A, Hansen S, Chaudhuri A. Exercise lowers pain threshold in chronic fatigue syndrome. Pain. 2004 Jun;109(3):497-9.
  57. ↑ 57.0 57.1 Meeus, Mira; Roussel, Nathalie A.; Truijen, Steven; Nijs, Jo (October 2010). "Reduced pressure pain thresholds in response to exercise in chronic fatigue syndrome but not in chronic low back pain: an experimental study". Journal of Rehabilitation Medicine. 42 (9): 884–890. doi:10.2340/16501977-0595. ISSN 1651-2081. PMID 20878051.
  58. ↑ 58.0 58.1 Van Oosterwijck, J.; Nijs, J.; Meeus, Mira; Lefever, I.; Huybrechts, L.; Lambrecht, L.; Paul, L. (2010). "Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study". J Intern Med. 268 (3): 265–78. doi:10.1111/j.1365-2796.2010.02228.x. PMID 20412374.
  59. ↑ Yunus MB. Editorial review: an update on central sensitivity syndromes and the issues of nosology and psychobiology. Curr Rheumatol Rev. 2015;11(2):70-85.
  60. ↑ Nijs J, Apeldoorn A, Hallegraeff H, Clark J, Smeets R, Malfliet A, et al. Low back pain: guidelines for the clinical classification of predominant neuropathic, nociceptive, or central sensitization pain. Pain Physician. 2015 May-Jun;18(3):E333-46.
  61. ↑ Sanchis MN, Lluch E, Nijs J, Struyf F, Kangasperko M. The role of central sensitization in shoulder pain: A systematic literature review. Semin Arthritis Rheum. 2015 Jun;44(6):710-6.
  62. ↑ Lluch E, Nijs J, Courtney CA, Rebbeck T, Wylde V, Baert I, et al. Clinical descriptors for the recognition of central sensitization pain in patients with knee osteoarthritis. Disabil Rehabil. 2017 Aug 2:1-10.
  63. ↑ Nijs J, Leysen L, Adriaenssens N, Aguilar Ferrándiz ME, Devoogdt N, et al. Pain following cancer treatment: Guidelines for the clinical classification of predominant neuropathic, nociceptive and central sensitization pain. Acta Oncol. 2016 Jun;55(6):659-63.
  64. ↑ Van Oosterwijck J, Nijs J, Meeus M, Paul L. Evidence for central sensitization in chronic whiplash: a systematic literature review. Eur J Pain. 2013 Mar;17(3):299-312.
  65. ↑ Nijs J, Torres-Cueco R, van Wilgen CP, Girbes EL, Struyf F, Roussel N, et al. Applying modern pain neuroscience in clinical practice: criteria for the classification of central sensitization pain. Pain Physician. 2014 Sep-Oct;17(5):447-57.
  66. ↑ 66.0 66.1 Nijs, Jo; Meeus, Mira; Van Oosterwijck, Jessica; Roussel, Nathalie; De Kooning, Margot; Ickmans, Kelly; Matic, Milica (May 2011). "Treatment of central sensitization in patients with 'unexplained' chronic pain: what options do we have?". Expert Opinion on Pharmacotherapy. 12 (7): 1087–1098. doi:10.1517/14656566.2011.547475. ISSN 1744-7666. PMID 21254866.
  67. ↑ 67.0 67.1 67.2 67.3 Nijs, Jo; Malfliet, Anneleen; Ickmans, Kelly; Baert, Isabel; Meeus, Mira (August 1, 2014). "Treatment of central sensitization in patients with 'unexplained' chronic pain: an update". Expert Opinion on Pharmacotherapy. 15 (12): 1671–1683. doi:10.1517/14656566.2014.925446. ISSN 1465-6566. PMID 24930805.
  68. ↑ 68.0 68.1 Meeus, Mira; Ickmans, Kelly; Clerck, Luc S. De; Moorkens, Greta; Hans, Guy; Grosemans, Sofie; Nijs, Jo (November 1, 2011). "Serotonergic Descending Inhibition in Chronic Pain: Design, Preliminary Results and Early Cessation of a Randomized Controlled Trial". In Vivo. 25 (6): 1019–1025. ISSN 0258-851X. PMID 22021700.
  69. ↑ "Prescribing Opioids for Chronic Pain". Medscape. Retrieved April 3, 2022.
  70. ↑ 70.0 70.1 Hermans, L; Nijs, J; Calders, P; De Clerck, L; Moorkens, G; Hans, G; Grosemans, S; Roman de Mettelinge, T; Tuynman, J; Meeus, M (2017). "Influence of morphine and naloxone on pain modulation in Rheumatoid Arthritis, Chronic Fatigue Syndrome/Fibromyalgia and controls: a double blind randomized placebo-controlled cross-over study". Pain Physician. 18. doi:10.1111/papr.12613. PMID 28722815.
  71. ↑ 71.0 71.1 Nijs, Jo; Crombez, Geert; Meeus, Mira; Knoop, Hans; Damme, Stefaan Van; Van Cauwenbergh, Deborah; Bleijenberg, Gijs (September 2012). "Pain in patients with chronic fatigue syndrome: time for specific pain treatment?". Pain Physician. 15 (5): E677–686. ISSN 2150-1149. PMID 22996861.
  72. ↑ Kindlon T. Educational programs for chronic fatigue syndrome need to take cognizance of the condition's abnormal response to exercise. Arch Phys Med Rehabil. 2011 Jun;92(6):1015; author reply 1015-6.
  73. ↑ 73.0 73.1 73.2 Nijs, Jo; Van Cauwenbergh, Deborah; De Kooning, Margot; Ickmans, Kelly (September 8, 2012). "Ignoring the evidence favouring exercise therapy for chronic fatigue syndrome is unethical and scientifically incorrect". European Journal of Clinical Investigation. 42 (11): 1257–1258. doi:10.1111/j.1365-2362.2012.02716.x. ISSN 0014-2972.
  74. ↑ Kos, D; Nijs, J; Meeus, M; Salhi, B. (2012). Chronische vermoeidheid: een praktische handleiding voor de revalidatie van kanker, MS, fibromyalgie en CVS (in Nederlands). Leuven: Acco.
  75. ↑ Abbi B and Natelson BH. Is chronic fatigue syndrome the same illness as fibromyalgia: evaluating the 'single syndrome' hypothesis. QJM. 2013 Jan;106(1):3-9.
  76. ↑ Nijs, Jo; De Becker, Pascale; De Meirleir, Kenny L.; Demanet, Christian; Vincken, Walter; Schuermans, Daniel; McGregor, Neil (2003). "Associations between bronchial hyperresponsiveness and immune cell parameters in patients with chronic fatigue syndrome". Chest. 123 (4). PMID 12684286.
  77. ↑ Nijs, Jo; Coomans, Danny; Nicolson, Garth L.; De Becker, Pascale; Christian, Demanet; De Meirleir, Kenny L. (2003). "Immunophenotyping Predictive of Mycoplasma Infection in Patients with Chronic Fatigue Syndrome?". Journal of Chronic Fatigue Syndrome. 11 (2). doi:10.1300/J092v11n02_05.
  78. ↑ Nijs, Jo; De Becker, Pascale; Demanet, Christian; McGregor, Neil; Englebienne, Patrick; Verhas, Michel; De Meirleir, Kenny L. (2003). "Monitoring a Hypothetical Channelopathy in Chronic Fatigue Syndrome: Preliminary Observations". Journal of Chronic Fatigue Syndrome. 11 (1): 117–133. doi:10.1300/J092v11n01_03.
  79. ↑ Nijs, Jo; Nicolson, Garth L. (2004). "Gulf War Veterans: Evidence for Chromosome Alterations and Their Significance". Journal of Chronic Fatigue Syndrome. 12 (1): 79–83. doi:10.1300/J092v12n01_06.
  80. ↑ Meeus, M; Nijs, J; Hermans, L; Goubert, D; Calders, P (September 2013). "The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: peripheral and central mechanisms as therapeutic targets?". Expert Opin Ther Targets. doi:10.1517/14728222.2013.818657. PMID 23834645.
  81. ↑ Nijs, J; Nees, A; Paul, L; De Kooning, M; Ickmans, K; Meeus, M; Van Oosterwijck, J (2014). "Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review". Exercise Immunology Review (20): 94-116. PMID 24974723.
  82. ↑ Nijs, J; Malfliet, A (2016). "Rehabilitation for patients with myalgic encephalomyelitis/chronic fatigue syndrome: time to extent the boundaries of this field". Journal of Intern Medicine. 279 (3): 265–7. doi:10.1111/joim.12431.
  83. ↑ Polli, Andrea; Van Oosterwijck, Jessica; Meeus, Mira; Lambrecht, Luc; Nijs, Jo; Ickmans, Kelly (October 16, 2018). "Exercise-induce hyperalgesia, complement system and elastase activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – a secondary analysis of experimental comparative studies". Scandinavian Journal of Pain. 19 (1): 183–192. doi:10.1515/sjpain-2018-0075. ISSN 1877-8879.
  84. ↑ Ickmans, Kelly; Lambrecht, Luc; Moorkens, Greta; Meeus, Mira; Paul, Lorna; Wandele, Inge De; Marusic, Uros; Nijs, Jo; Oosterwijck, Jessica Van (January 18, 2019). "Relationship Between Exercise-induced Oxidative Stress Changes and Parasympathetic Activity in Chronic Fatigue Syndrome: An Observational Study and in Patients and Healthy Subjects". Clinical Therapeutics. doi:10.1016/j.clinthera.2018.12.012. ISSN 0149-2918. PMID 30665828.
  85. ↑ Nijs, Jo; Leysen, Laurence; Vanlauwe, Johan; Logghe, Tine; Ickmans, Kelly; Polli, Andrea; Malfliet, Anneleen; Coppieters, Iris; Huysmans, Eva (November 2, 2019). "Treatment of central sensitization in patients with chronic pain: time for change?". Expert Opinion on Pharmacotherapy. 20 (16): 1961–1970. doi:10.1080/14656566.2019.1647166. ISSN 1465-6566. PMID 31355689.
  86. ↑ Polli, Andrea; Ghosh, Manosij; Bakusic, Jelena; Ickmans, Kelly; Monteyne, Dora; Velkeniers, Brigitte; Bekaert, Bram; Godderis, Lode; Nijs, Jo (October 7, 2020). "DNA Methylation and Brain‐Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia". Arthritis & Rheumatology. 72 (11): 1936–1944. doi:10.1002/art.41405. ISSN 2326-5191.
  87. ↑ Van Oosterwijck, Jessica; Marusic, Uros; De Wandele, Inge; Meeus, Mira; Paul, Lorna; Lambrecht, Luc; Moorkens, Greta; Danneels, Lieven; Nijs, Jo (January 2021). "Reduced Parasympathetic Reactivation during Recovery from Exercise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". Journal of Clinical Medicine. 10 (19): 4527. doi:10.3390/jcm10194527. ISSN 2077-0383.
  88. ↑ Nijs, Jo; George, Steven Z.; Clauw, Daniel J.; Fernández-de-las-Peñas, César; Kosek, Eva; Ickmans, Kelly; Fernández-Carnero, Josué; Polli, Andrea; Kapreli, Eleni; Huysmans, Eva; Cuesta-Vargas, Antonio I. (May 1, 2021). "Central sensitisation in chronic pain conditions: latest discoveries and their potential for precision medicine". The Lancet Rheumatology. 3 (5): e383–e392. doi:10.1016/S2665-9913(21)00032-1. ISSN 2665-9913.
  89. ↑ Nijs, Jo; George, Steven Z.; Clauw, Daniel J.; Fernández-de-las-Peñas, César; Kosek, Eva; Ickmans, Kelly; Carnero, Josué Fernández; Polli, Andrea; Kapreli, Eleni; Huysmans, Eva; Cuesta-Vargas, Antonio I. (August 1, 2021). "Central sensitisation: causes, therapies, and terminology – Authors' reply". The Lancet Rheumatology. 3 (8): e548–e549. doi:10.1016/S2665-9913(21)00182-X. ISSN 2665-9913. PMID 28339438.

cognition Thought processes, including attention, reasoning, and memory.

Concerning living organisms, such as cells or the human body.[1]  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

(HR) - the number of times the heart beats within a certain time period, usually a minute[2]

heart rate (HR) - the number of times the heart beats within a certain time period, usually a minute

graded exercise therapy (GET) - A gradual increase in exercise or activity, according to a pre-defined plan. Focuses on overcoming the patient's alleged unhelpful illness beliefs that exertion can exacerbate symptoms, rather than on reversing physical deconditioning. Considered controversial, and possibly harmful, in the treatment or management of ME. One of the treatment arms of the controversial PACE trial.

See Graded exercise therapy.

See ME/CFS.

Bias in research is "a systematic deviation of an observation from the true clinical state".[3] (Learn more: me-pedia.org)

bias Bias in research is "a systematic deviation of an observation from the true clinical state". (Learn more: me-pedia.org)

PACE trial A controversial study which claimed that CBT and GET were effective in treating "CFS/ME", despite the fact that its own data did not support this conclusion. Its results and methodology were widely disputed by patients, scientists, and the peer-reviewed scientific literature.

pacing The practice of staying within one's "energy envelope" or personal limit by combining periods of activity with periods of rest or avoiding exerting beyond a certain level. ME/CFS patients use pacing to avoid or reduce post-exertional malaise (PEM). Some patients use a heart rate monitor to help with pacing.

kinesiophobia excessive and irrational fear of physical movement due to fear of painful injury or reinjury. (Learn more: me-pedia.org)

kinesiophobia excessive and irrational fear of physical movement due to fear of painful injury or reinjury. (Learn more: me-pedia.org)

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

See post-exertional malaise.

(CBF) - the amount of blood that goes through the arterial tree in the brain in a given amount of time[4]

cerebral blood flow (CBF) - the amount of blood that goes through the arterial tree in the brain in a given amount of time

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

central nervous system (CNS) - One of the two parts of the human nervous system, the other part being the peripheral nervous system. The central nervous system consists of the brain and spinal cord, while the peripheral nervous system consists of nerves that travel from the central nervous system into the various organs and tissues of the body.

endogenous Growing or originating from within an organism.

Growing or originating from within an organism.[5]

endogenous Growing or originating from within an organism.

A chemical that reduces or helps block the activity of another chemical in the body. For example, most antihistamines are H1 antagonists because they block the H1 histamine receptor, which helps relieve allergy symptoms. The opposite of an agonist.[6][7]

antagonist A chemical that reduces or helps block the activity of another chemical in the body. For example, most antihistamines are H1 antagonists because they block the H1 histamine receptor, which helps relieve allergy symptoms. The opposite of an agonist.

antagonist A chemical that reduces or helps block the activity of another chemical in the body. For example, most antihistamines are H1 antagonists because they block the H1 histamine receptor, which helps relieve allergy symptoms. The opposite of an agonist.

physiological Concerning living organisms, such as cells or the human body.  Physio logical (as in physio) is not to be confused with psych ological (emotional stress).

cognition Thought processes, including attention, reasoning, and memory.

biopsychosocial model (BPS) - A school of thought, usually based in psychology, which claims illness and disease to be the result of the intermingling of biological, psychological and social causes. (Learn more: me-pedia.org)

etiology The cause of origin, especially of a disease.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

See Centers for Disease Control and Prevention.

biopsychosocial model (BPS) - A school of thought, usually based in psychology, which claims illness and disease to be the result of the intermingling of biological, psychological and social causes. (Learn more: me-pedia.org)

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

postural orthostatic tachycardia syndrome (POTS) - A form of orthostatic intolerance where the cardinal symptom is excessive tachycardia due to changing position (e.g. from lying down to sitting up).

double blinded trial A clinical trial is double blinded if neither the participants nor the researchers know which treatment group they are allocated to until after the results are interpreted. This reduces bias. (Learn more: www.nottingham.ac.uk)

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

randomized controlled trial (RCT) - A trial in which participants are randomly assigned to two groups, with one group receiving the treatment being studied and a control or comparison group receiving a sham treatment, placebo, or comparison treatment.

double blinded trial A clinical trial is double blinded if neither the participants nor the researchers know which treatment group they are allocated to until after the results are interpreted. This reduces bias. (Learn more: www.nottingham.ac.uk)

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

cerebral 1. of or relating to the brain or the intellect 2. of, relating to, affecting, or being the cerebrum.

heart rate variability (HRV) - A measurement of the variability of the heart rate over time. When the heart rate is consistent, there will be a low heart rate variability. When the heart rate is constantly changing, there will be a high heart rate variability. Heart rate variability is often used by ME/CFS patients to monitor their autonomic nervous system, as high heart rate variability is associated with the sympathetic nervous system and low heart rate variability is associated with the parasympathetic nervous system.

stress Stress can by either physical or psychological, or both. Stress is either 1) a state of emotional or psychological strain or 2) the physical stress (pressure or tension) that a physical object such the human body is placed under, e.g., a stress test is a medical test that monitors the cardiovascular system during strenuous exercise.

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