INTRODUCTION Ankylosing spondylitis is a chronic inflammatory disease that primarily affects the sacroiliac joints and the spine, leading to stiffness, pain, and functional limitation. The rationale for multimodal ozone therapy includes: GAET, topical application of a rechargeable biodynamic and transdermal tape with gradual release of Ozoile (stable ozonides), and infiltrative ozone therapy. The protocol is proposed to modulate inflammation, control pain, and improve quality of life. Case Presentation: A 48-year-old patient with ankylosing spondylitis came to our for poorly controlled pain, insomnia, confusional state, and hallucinations. The patient had been on Methotrexate and Fentanyl TTS 50 µg/h for 2 years. Due to insufficient analgesic response and adverse effects, an integrated treatment plan was initiated with multimodal ozone therapy and equianalgesic transdermal buprenorphine (70 µg/h). The objective of this study is to highlight the specific analgesic action of multimodal ozone therapy, considering the high baseline pain levels and disease impact1. MATERIALS AND METHODS Outcomes evaluated: Pain (VAS), physical function (BASFY index), sleep quality and side effects were monitored through structured clinical interviews. Clinical controls were evaluated weekly for 60 days. Treatment protocol: • GAET: 1 session/week, 100 ml of ozone at 25 µg/ml in 100 ml of blood (1st session), 30 µg/ml (subsequent sessions); • Transdermal tape: 2 applications/week of rechargeable taping with microcells for gradual release of Ozoile; • Ozone infiltrations: 1 infiltration/week in the lumbosacral region (12 µg) RESULTS VAS score dropped from 8 to 6 after the first session, and progressively to 2. Insomnia, confusion, and hallucinations resolved. BASFI improved from 120 to 50. CONCLUSIONS Improvements in reduction of pain, sleep quality, and resolution of the confusional state and hallucinations, occurred in close temporal correlation with the start of treatment. GAET decreased disease activity1 and acted by modulating systemic inflammation and oxidative stress without any side effects. The application of Ozoile-based patches contributed to a prolonged local analgesic effect, improving peripheral symptoms and subjective pain perception. Ozone infiltrations provided a targeted anti-inflammatory and analgesic effect at the site of maximum pathological activity2. Furthermore, the combination of multimodal ozone therapy with buprenorphine TTS produced a synergistic effect, enhancing pain control, considering that, at the same equianalgesic dose, buprenorphine, as a partial agonist of µ-opioid receptors, has lower analgesic efficacy compared to fentanyl, which acts as a full agonist and is more potent in terms of pain relief3. Therefore, in the described case, multimodal ozone therapy performed an anti-inflammatory action and contributed to a significant attenuation of painful symptoms and an improvement in the patient's quality of life.
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