Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation.

Evidence Atlas

Jonsjö, Martin A, Åström, Jenny, Jones, Michael P et al. · Brain, behavior, & immunity - health · 2020 · DOI

Quick Summary

This study compared how 'sick' people with ME/CFS and chronic pain feel compared to other groups. Researchers found that ME/CFS and chronic pain patients reported feeling as sick as healthy people who were given a bacterial toxin to trigger temporary inflammation. These high levels of sickness feelings were similar across both conditions and higher than what primary care patients reported, suggesting that the persistent sickness sensation in ME/CFS and chronic pain may involve similar biological mechanisms related to inflammation and how the brain processes illness signals.

Why It Matters

This research provides objective evidence that the persistent, pervasive sickness sensation experienced by ME/CFS patients is comparable to that induced by acute immune activation, supporting the hypothesis that immune-to-brain signaling and inflammatory pathways may be centrally involved in ME/CFS pathophysiology. Understanding sickness behavior as a core feature rather than secondary consequence could shift clinical approaches to assessment and treatment and validate patients' experiences of illness severity.

Observed Findings

ME/CFS patients reported sickness behavior scores of 16.1, nearly identical to LPS-injected individuals (16.3) and significantly higher than healthy controls (3.6) and general population (5.4).
Chronic pain patients also reported sickness behavior scores of 16.1, matching ME/CFS patients and LPS-injected groups.
Both ME/CFS and chronic pain patients showed significantly higher sickness behavior than primary care patients (10.7).
Higher sickness behavior was associated with poorer self-rated health and functioning across groups, though this relationship was less pronounced in ME/CFS and chronic pain populations.
The similarity between ME/CFS, chronic pain, and experimental inflammation groups suggests shared biological mechanisms underlying sickness sensation.

Inferred Conclusions

Patients with ME/CFS and chronic pain experience sickness behavior at levels comparable to acute immune activation, suggesting immune-to-brain interactions may contribute to core symptoms in both conditions.
Sickness behavior appears to be a shared feature across ME/CFS and chronic pain, potentially indicating overlapping pathophysiological mechanisms.
The weaker association between sickness behavior and self-rated functioning in ME/CFS and chronic pain than in the general population suggests that chronically ill patients may have adapted or that sickness behavior is a more fundamental feature of these diseases.
Immulogical and neurobiological mechanisms, rather than purely psychological factors, warrant further investigation as contributors to symptom severity in these populations.

What This Study Does Not Prove

This study does not prove that inflammation causes ME/CFS or that sickness behavior is the primary mechanism of disease. The cross-sectional design cannot establish causality or directionality—elevated sickness behavior could result from underlying pathology rather than causing it. The small sample size for ME/CFS (n=38) limits generalizability, and the study cannot identify which specific immune pathways or brain mechanisms drive these feelings in chronic conditions.

Metadata

DOI: 10.1016/j.bbih.2019.100028
PMID: 38377418
Review status: Editor reviewed
Evidence level: Single-study or moderate support from human research
Last updated: 12 April 2026

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 →

Evidence Atlas

Patients with ME/CFS (Myalgic Encephalomyelitis/Chronic Fatigue Syndrome) and chronic pain report similar level of sickness behavior as individuals injected with bacterial endotoxin at peak inflammation.

Quick Summary

Why It Matters

Observed Findings

Inferred Conclusions

What This Study Does Not Prove

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