Nijs, Jo, Van de Velde, Bart, De Meirleir, Kenny · Medical hypotheses · 2005 · DOI
This study proposes a theory about why ME/CFS patients experience widespread pain. The researchers suggest that a molecule called nitric oxide may cause the central nervous system (the brain and spinal cord) to become overly sensitive, amplifying pain signals throughout the body. They propose that viral infections or other pathogens associated with ME/CFS may trigger this chain reaction, and that behaviors like catastrophizing or avoiding activity may either contribute to or result from this heightened sensitivity.
Pain is a major driver of disability in ME/CFS, accounting for over a quarter of activity limitations. Understanding the biological mechanisms underlying widespread pain could lead to targeted treatments and help distinguish ME/CFS pain from other chronic pain conditions.
This is a theoretical hypothesis paper, not an empirical study with patient data or experimental evidence. It does not prove that nitric oxide directly causes central sensitization in ME/CFS patients, nor does it establish which direction causality flows between behavioral changes and nervous system sensitization. The proposal remains speculative and requires experimental validation.
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
Nijs, Jo, Van de Velde, Bart, & De Meirleir, Kenny (2005). Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation?. Medical hypotheses. https://doi.org/10.1016/j.mehy.2004.07.037
BibTeX
@article{mecfsatlas-nijs-2005-pain-patients,
author = {Nijs, Jo and Van de Velde, Bart and De Meirleir, Kenny},
title = {Pain in patients with chronic fatigue syndrome: does nitric oxide trigger central sensitisation?},
journal = {Medical hypotheses},
year = {2005},
doi = {10.1016/j.mehy.2004.07.037},
note = {PubMed: 15617866},
url = {https://www.mecfsatlas.com/evidence/nijs-2005-pain-patients},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/nijs-2005-pain-patients
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