Adrenergic dysfunction in patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia: A systematic review and meta-analysis.

Ishtiaq Ahmed, Lode Godderis, Andrea Polli, Kelly Ickmans, Jo Nijs, Jente Van Campenhout, Arne Wyns, Jolien Hendrix, Lara Fanning, Madhura Shekhar Patil, Emma Richter, Rembert Mertens

Journal: European journal of clinical investigation 2024;55(1):e14318

PMID: 39319943

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Abstract

BACKGROUND

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.

METHODS

A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta-analyses were performed using R statistical software.

RESULTS

This meta-analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31-.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06-1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18-.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02-.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03-.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [-.47 to -.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = -.79 [-1.27 to -.30]; Z = -3.14; p < .01).

CONCLUSION

This systematic review and meta-analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM.

Address: Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.; Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Leuven, Belgium.; Flanders Research Foundation-FWO, Brussels, Belgium.; Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Leuven, Belgium.; Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.; Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Leuven, Belgium.; Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.; Faculty of Physical Education and Physiotherapy, Department Movement and Nutrition for Health and Performance, Vrije Universiteit Brussel, Brussels, Belgium.; Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.; Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.; Flanders Research Foundation-FWO, Brussels, Belgium.; Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium.; Movement & Nutrition for Health & Performance Research Group (MOVE), Department of Movement and Sport Sciences, Vrije Universiteit Brussel, Brussels, Belgium.; Department of Internal Medicine, Vrije Universiteit Brussel, University Hospital Brussels, Brussels, Belgium.; Pain in Motion (PiM) international research group, Department of Physiotherapy, Human Physiology and Anatomy, Faculty of Rehabilitation Sciences & Physiotherapy, Vrije Universiteit Brussel, Brussels, Belgium.; Department of Physical Medicine and Physiotherapy, University Hospital Brussels, Brussels, Belgium.; Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.; Department of Public Health and Primary Care, Centre for Environment & Health, KU Leuven, Leuven, Belgium.; External Service for Prevention and Protection at Work, IDEWE, Heverlee, Belgium.

DOI: 10.1111/eci.14318