Yasui, Masaya, Menjyo, Yuki, Tokizane, Kyohei et al. · Journal of neuroinflammation · 2019 · DOI
This study used rats exposed to chronic stress to understand why ME/CFS patients experience widespread pain without obvious tissue damage. Researchers found that stress caused sensory nerve fibers (proprioceptors) that detect body position to become overactive, which then triggered immune cells in the spinal cord called microglia to activate and cause pain. When they immobilized the ankle to reduce proprioceptor signaling, both the immune activation and pain behavior decreased.
This study identifies a testable mechanistic pathway linking chronic stress to centralized pain in ME/CFS—proprioceptor hyperactivation driving microglial-mediated neuroinflammation—without requiring peripheral tissue damage. These findings could inform new therapeutic targets (proprioceptor modulation, microglial inhibition) and help explain why pain persists despite normal inflammatory markers in many patients.
This rat model study does not prove that proprioceptor dysfunction is the primary driver of human ME/CFS pain, nor does it establish whether this mechanism applies to all patients with CFS or fibromyalgia. The study demonstrates association and suggests causality in one specific stress paradigm but does not rule out other contributing neuroinflammatory pathways or validate treatment interventions in humans.
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
Yasui, Masaya, Menjyo, Yuki, Tokizane, Kyohei, Shiozawa, Akiko, Tsuda, Makoto, Inoue, Kazuhide, et al. (2019). Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome.. Journal of neuroinflammation. https://doi.org/10.1186/s12974-019-1456-x
BibTeX
@article{mecfsatlas-yasui-2019-hyperactivation-proprioceptors,
author = {Yasui, Masaya and Menjyo, Yuki and Tokizane, Kyohei and Shiozawa, Akiko and Tsuda, Makoto and Inoue, Kazuhide and Kiyama, Hiroshi},
title = {Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome.},
journal = {Journal of neuroinflammation},
year = {2019},
doi = {10.1186/s12974-019-1456-x},
note = {PubMed: 30927920},
url = {https://www.mecfsatlas.com/evidence/yasui-2019-hyperactivation-proprioceptors},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/yasui-2019-hyperactivation-proprioceptors
Contribute
Private, reviewed by a human. Not a public comment thread.