Evengard, B, Nilsson, C G, Lindh, G et al. · Pain · 1998 · DOI
Researchers measured a pain-signaling chemical called substance P in the spinal fluid of 15 people with ME/CFS. They found that all the ME/CFS patients had normal levels of this chemical. This is important because fibromyalgia—a condition with similar symptoms—typically shows elevated substance P levels. This finding suggests that ME/CFS and fibromyalgia may be caused by different biological problems, even though patients experience some overlapping symptoms.
This study provides early evidence that ME/CFS has a different biological basis than fibromyalgia, which could eventually guide more targeted treatments for each condition. It validates that ME/CFS is a distinct disease entity rather than a variant of fibromyalgia, supporting the need for disease-specific research and clinical approaches.
This study does not identify what actually causes ME/CFS or prove that substance P plays no role in ME/CFS pathophysiology overall—only that CSF levels are not consistently elevated as they are in fibromyalgia. It does not explain why the two conditions have overlapping symptoms or rule out other shared biological mechanisms. A single normal biomarker does not prove ME/CFS involves no neuropathic pain processes.
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
Evengard, B, Nilsson, C G, Lindh, G, Lindquist, L, Eneroth, P, Fredrikson, S, et al. (1998). Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome.. Pain. https://doi.org/10.1016/S0304-3959(98)00134-1
BibTeX
@article{mecfsatlas-evengard-1998-chronic-fatigue,
author = {Evengard, B and Nilsson, C G and Lindh, G and Lindquist, L and Eneroth, P and Fredrikson, S and Terenius, L and Henriksson, K G},
title = {Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome.},
journal = {Pain},
year = {1998},
doi = {10.1016/S0304-3959(98)00134-1},
note = {PubMed: 9839828},
url = {https://www.mecfsatlas.com/evidence/evengard-1998-chronic-fatigue},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/evengard-1998-chronic-fatigue
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