Dhondt, Evy, Danneels, Lieven, Rijckaert, Johan et al. · European journal of pain (London, England) · 2021 · DOI
This study tested whether being physically or mentally tired changes how the body's spinal cord responds to pain signals. Researchers measured a reflex that happens in the spinal cord when stimulated with electrical pulses to a nerve in the leg, both before and after participants either rested, did tiring leg exercises, or completed a difficult mental task. They found that low-to-moderate levels of fatigue—whether physical or mental—did not change this spinal reflex, suggesting the body's pain-dampening systems stay stable even when tired.
ME/CFS patients experience profound, often disabling fatigue and frequently report pain symptoms, yet the relationship between fatigue and pain processing at the spinal level remains poorly understood. This mechanistic study contributes foundational knowledge about whether fatigue dampens pain-inhibitory pathways, which has implications for understanding why some pain-focused treatments may remain effective even when patients are severely fatigued.
This study does not demonstrate how severe or prolonged fatigue—as seen in ME/CFS—affects pain processing; it only examined low-to-moderate experimental fatigue in healthy people. It does not prove that pain and fatigue are completely independent in ME/CFS patients, nor does it establish causation between any variables. The findings in healthy controls may not translate to patients with chronic fatigue syndrome, where neurophysiological processes may be fundamentally altered.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Dhondt, Evy, Danneels, Lieven, Rijckaert, Johan, Palmans, Tanneke, Van Oosterwijck, Sophie, & Van Oosterwijck, Jessica (2021). Does muscular or mental fatigue have an influence on the nociceptive flexion reflex? A randomized cross-over study in healthy people.. European journal of pain (London, England). https://doi.org/10.1002/ejp.1763
BibTeX
@article{mecfsatlas-dhondt-2021-does-muscular,
author = {Dhondt, Evy and Danneels, Lieven and Rijckaert, Johan and Palmans, Tanneke and Van Oosterwijck, Sophie and Van Oosterwijck, Jessica},
title = {Does muscular or mental fatigue have an influence on the nociceptive flexion reflex? A randomized cross-over study in healthy people.},
journal = {European journal of pain (London, England)},
year = {2021},
doi = {10.1002/ejp.1763},
note = {PubMed: 33721359},
url = {https://www.mecfsatlas.com/evidence/dhondt-2021-does-muscular},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/dhondt-2021-does-muscular
Contribute
Private, reviewed by a human. Not a public comment thread.