Abstract
Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Fibromyalgia (FM) are complex multisystem conditions with disabling symptoms associated with functionally impairing fatigue post-exertional malaise (PEM) and/or widespread chronic pain, which greatly affects the quality of life. These conditions are poorly understood, therefore, further biological research is critical. Inflammatory abnormalities have been linked to the symptoms experienced. This thesis aims to investigate neural and peripheral response, including differential gene expression, to a mild inflammatory challenge. The findings may elucidate biological mechanisms contributing to the experience of pain and fatigue in these patient groups.Methods: The study included 55 patients (22 ME/CFS, 18 FM and 15 ME/CFS comorbid with FM) and 22 healthy controls. After screening, all underwent an inflammatory challenge (typhoid vaccine) and a placebo (saline injection) during two separate visits. Blood samples were collected pre- and 4 hours post injection. Participants underwent physiological and psychological challenges, MRI scanning, and completed subjective painand fatigue questionnaires during each visit. Plasma samples collected were used to determine interleukine-6 (IL-6) concentration, whole blood PAXgene samples were used for RNA-sequencing, and MRI data were subject to structural and functional analysis.
Results: Patients had a higher level of inflammatory markers in the blood at baseline compared to controls but were not more sensitive to the inflammatory challenge. Differential gene expression analysis suggested there may be dysregulation of the ATP metabolic process in ME/CFS patients. The viral gene expression pathway was upregulated in ME/CFS patients compared to controls but not the FM patients. There was an association between fatigue and the microstructure and functioning of the posterior cingulate. However, no significant differences were found in resting-state fMRI between the patients and controls, both before and after the inflammatory challenge.
Conclusion: This study presented evidence of potential biological differences between ME/CFS patients, FM patients and healthy individuals, shedding light on the complex pathophysiology of these conditions. The findings indicated the need for further research to elucidate the role of inflammation and explore distinct gene expression profiles that may differentiate ME/CFS and FM. Identifying reliable diagnostic biomarkers and addressing study limitations, such as controlling lifestyle factors, will be crucial for advancing future research. Collaborative efforts, multimodal analysis, and longitudinal studies will contribute to a deeper understanding of ME/CFS and FM, potentially leading to improved diagnostic and therapeutic approaches.
| Date of Award | 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Jessica Eccles (Supervisor) |