Reviews
Oxygen-ozone autohaemotherapy in fibromyalgia: oxidative stress, Nrf2 activation, small fibre neuropathy and a critical narrative review of the evidence
R. Casale1, J. Bernatoniene2, K. Petrikonis3, D. Fornasari4, P. Sarzi-Puttini5, G. Varrassi6
- Opusmedica, Persons Care & Research NPO, Piacenza, Italy. robertocasale@opusmedica.org
- Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Lithuanian University of Health Sciences, Kaunas, Lithuania.
- Department of Neurology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
- Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Italy.
- Department of Biomedical and Clinical Sciences, University of Milan; and Rheumatology Unit, IRCCS Ospedale Galeazzi-Sant’Ambrogio, Milan, Italy.
- Fondazione Paolo Procacci, Roma, Italy; and College of Medicine, University of Baghdad, Iraq.
CER19793
2026 Vol.44, N°6
PI 1208, PF 1216
Reviews
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PMID: 42328949 [PubMed]
Received: 10/02/2026
Accepted : 28/05/2026
In Press: 22/06/2026
Published: 22/06/2026
Abstract
Fibromyalgia (FM) is a chronic pain disorder marked by widespread pain and significant impairment of daily life. Despite evolving diagnostic criteria and recognition as a primary chronic pain condition, current treatments yield limited success, and underlying mechanisms remain under investigation. This narrative review focuses on oxygen-ozone autohaemotherapy (O2-O3-AHT) as a potential intervention for FM, evaluating its biological rationale and possible mechanisms of action. The therapeutic interest in O2-O3-AHT centres on its capacity to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, reduce oxidative stress, improve mitochondrial function, and address small fibre pathology. The review employed a structured narrative synthesis, adhering to SANRA guidelines to ensure methodological rigor and transparency. Comprehensive literature searches included peer-reviewed articles published in English from 2015 to 2025. Evidence suggests that O2-O3-AHT may provide multi-target benefits for FM patients by modulating redox balance, enhancing mitochondrial resilience, and potentially alleviating neuropathic components related to small fibre dysfunction. Clinical studies, though limited and often heterogeneous, report improvements in pain, sleep quality, fatigue, and overall functional status in FM patients treated with O2-O3-AHT. Biomarker analyses further support reduced oxidative stress and inflammatory mediators post-intervention. However, the variability in treatment protocols, sample sizes, and outcome measures across studies complicates definitive conclusions about efficacy and safety. O2-O3-AHT represents a promising, mechanism-based approach to FM management, particularly for patients unresponsive to conventional therapies. Its ability to target central and peripheral biological processes aligns with the complex pathophysiology of FM. However, the current evidence base is restricted by methodological inconsistencies and a paucity of large, high-quality randomised trials. Future research should prioritise standardised protocols, robust clinical endpoints, and long-term safety assessment to validate the role of O2-O3-AHT in FM treatment. Until then, its use should be considered experimental and guided by careful patient selection and monitoring.
