McEwen, Bruce S, Kalia, Madhu · Metabolism: clinical and experimental · 2010 · DOI
This review explores how stress hormones (corticosteroids) and the body's stress response system affect chronic pain conditions, including ME/CFS. The authors explain that these hormones can have surprising and contradictory effects—sometimes reducing pain, sometimes increasing it—depending on the dose and where they act in the body. They examine how chronic stress and nervous system changes in conditions like ME/CFS, fibromyalgia, and IBS may be linked to pain through brain changes and immune system activity.
This review directly addresses ME/CFS as a stress-related condition involving HPA axis dysfunction and chronic pain, proposing mechanistic links between neuroendocrine dysregulation and central sensitization. Understanding how stress hormones paradoxically affect pain may explain why standard pain treatments are ineffective in ME/CFS and could guide development of HPA-targeted interventions. The framework connecting allostatic load to pain generation is particularly relevant for post-exertional malaise and symptom exacerbation in ME/CFS.
This review does not provide empirical evidence that corticosteroid dysfunction directly causes ME/CFS pain or establishes causality—it proposes mechanistic associations based on existing literature. The review does not demonstrate whether restoring HPA axis function would improve pain in ME/CFS patients, nor does it clarify which steroid dose ranges or timing would be therapeutic versus harmful. It does not establish that ME/CFS patients have demonstrable steroid abnormalities versus other chronic pain populations.
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
McEwen, Bruce S & Kalia, Madhu (2010). The role of corticosteroids and stress in chronic pain conditions.. Metabolism: clinical and experimental. https://doi.org/10.1016/j.metabol.2010.07.012
BibTeX
@article{mecfsatlas-mcewen-2010-role-corticosteroids,
author = {McEwen, Bruce S and Kalia, Madhu},
title = {The role of corticosteroids and stress in chronic pain conditions.},
journal = {Metabolism: clinical and experimental},
year = {2010},
doi = {10.1016/j.metabol.2010.07.012},
note = {PubMed: 20837196},
url = {https://www.mecfsatlas.com/evidence/mcewen-2010-role-corticosteroids},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-27. https://www.mecfsatlas.com/evidence/mcewen-2010-role-corticosteroids
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