Wakatsuki, Koji, Kiryu-Seo, Sumiko, Yasui, Masaya et al. · Journal of neuroinflammation · 2024 · DOI
Researchers used mice exposed to repeated cold stress to study how chronic pain develops, similar to fibromyalgia. They found that sensory nerve cells (proprioceptors) become overactive and trigger immune cells in the nervous system called microglia to become inflamed. When they reduced microglial activity with a drug, the pain improved, suggesting that this immune activation along nerve pathways may be a key driver of long-lasting pain.
This research identifies a potential shared biological mechanism—proprioceptor hyperactivation triggering microglial inflammation—that could underlie chronic pain in both fibromyalgia and ME/CFS. The finding that blocking microglial activation reduces pain provides a testable therapeutic target that could benefit both conditions. Understanding this mechanism may lead to new treatment approaches for the chronic pain experienced by many ME/CFS patients.
This animal study does not prove that proprioceptor-microglial activation is the sole cause of chronic pain in human ME/CFS or fibromyalgia patients. The repeated cold stress model, while useful, may not fully replicate the complex etiology of these conditions in humans. Additionally, findings in mice do not guarantee that the same mechanisms operate identically in human nervous systems or that drugs effective in mice will be safe and effective in patients.
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
Wakatsuki, Koji, Kiryu-Seo, Sumiko, Yasui, Masaya, Yokota, Hiroki, Kida, Haruku, Konishi, Hiroyuki, et al. (2024). Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice.. Journal of neuroinflammation. https://doi.org/10.1186/s12974-024-03018-6
BibTeX
@article{mecfsatlas-wakatsuki-2024-repeated-cold,
author = {Wakatsuki, Koji and Kiryu-Seo, Sumiko and Yasui, Masaya and Yokota, Hiroki and Kida, Haruku and Konishi, Hiroyuki and Kiyama, Hiroshi},
title = {Repeated cold stress, an animal model for fibromyalgia, elicits proprioceptor-induced chronic pain with microglial activation in mice.},
journal = {Journal of neuroinflammation},
year = {2024},
doi = {10.1186/s12974-024-03018-6},
note = {PubMed: 38238800},
url = {https://www.mecfsatlas.com/evidence/wakatsuki-2024-repeated-cold},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/wakatsuki-2024-repeated-cold
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