Ozone in Pain Medicine – Modern-day Asclepius
Authors: Chansoria Mayank , Saluja Shinu Kaur , Verma Aditi , Mamtani Bhawna , Rath Abhilash , Sethi Akshita , Hussain Parveen , Tanaya Vesarapu Surya 
Published: February 2025

Ozone therapy, utilizing medical ozone, has gained attention for its therapeutic potential in conditions characterized by chronic hypoxia, inflammation, and redox imbalance. Initially discovered in 1839, ozone offers various medical applications due to its properties as a potent oxidizing molecule. Despite its instability, ozone has been utilized in medical practice for over a century, demonstrating bactericidal, anti-inflammatory, and circulatory stimulating properties. Injected ozone rapidly reacts with water and fatty acids in human fluids and tissues, leading to the formation of hydrogen peroxide and lipid ozonation products. This reaction activates the NRF2 (nuclear factor erythroid 2–related factor 2) pathway, promoting antioxidant systems and inducing an anti-inflammatory effect. Additionally, ozone inactivates proteolytic enzymes, promotes fibroblast proliferation, and aids in tissue regeneration. Ozone therapy stimulates oxygen metabolism, modulates the immune system, and exhibits antimicrobial properties. It promotes tissue repair, reduces inflammation and edema, and enhances epithelialization and collagen deposition. Moreover, ozone therapy increases ATP and 2,3-DPG (DiPhosphoGlycerate) levels, improves oxygen metabolism, and enhances energy production. Ozone therapy can be administered topically, infiltratively, or systemically. Topical applications exploit ozone's germicidal properties, while infiltrative techniques are useful for musculoskeletal disorders. Systemic administration includes autohemotherapy, direct intravenous gas injection, and rectal insufflation, each offering unique therapeutic benefits. Standardized protocols for ozone therapy dosage are lacking, with amounts typically based on the extent of injury or joint cavity size. Concentrations range from 4 to 30x103 μg/ml, with the number of sessions varying depending on individual response. Ozone therapy has shown promise in treating knee osteoarthritis, shoulder pathology, lumbar disc herniation, rheumatoid arthritis, lower back pain, fibromyalgia, cancer, and stroke. Studies demonstrate its efficacy in reducing pain, promoting tissue repair, and enhancing overall well-being. Ozone therapy is generally safe, with rare adverse effects. Adverse effects depend on the administration route and may include abdominal distension, hypoesthesia, or transient worsening of pain. Absolute contraindications include severe glucose-6 phosphate dehydrogenase deficiency, while relative contraindications involve specific medical conditions such as hyperthyroidism or thrombocytopenia. Ozone therapy offers a promising adjunctive treatment option for various medical conditions, showcasing beneficial effects across pain management, tissue repair, and immune modulation. Despite the need for standardized protocols and further research, ozone therapy holds potential for integration into mainstream medical care, offering a conservative and minimally invasive treatment option for patients with chronic pain and inflammatory conditions.