Introduction and Mechanism of action
The Oxidizing property of ozone as a soluble gas is greatly responsible for it’s therapeutic action. Ozone, on contact with biological fluids leads to the formation of Reactive oxygen species (ROS)and Lipid oxidation products.(LOP)[1] These in turn trigger the formation of cytokines, proteins and erythrocytes( Red Blood Cells) by reacting with leukocytes(White Blood Cells). The result of these reactions is increased oxygen supply in the tissue.
The molecules of ROS and LOP , at physiological concentrations help in the biochemical regulation of Inflammation.[2] LOPs bring about a sense of well being as they stimulate the CNS and the Endocrine system to boost neurotransmitter release, hormonal production and metabolism.[2] A study observing the ozonation of samples of platelet rich plasma noted the increase in the release of IL-8(Interleukin-8). IL-8 helps in releasing the leukocytes from the circulation into the tissues to facilitate phagocytosis of bacteria and necrotic tissue of ulcers.[3] An increase in growth factors such as Platelet Derived Growth Factor(PDGF) and Transforming Growth Factor beta was also observed.
A study conducted by Re et al showed that ozone was capable of bringing about preservation and increase in endogenous antioxidant systems.[4]
Ozone can be administered via the intrarticular, peri-articular or the percutaneous route.
It is widely regarded as highly safe procedure with many proponents convinced of it’s analgesic and anti inflammatory properties after using Ozone on a multitude of patients.
Ozone therapy works by raising the pain threshold via activation of the antinociceptive apparatus which in turn is governed by serotonin and endogenous opioids. Ozone increases the vascularity by enriching the tissues with oxygen thus creating a favourable
Environment for neoangiogenesis. Ozone therapy is believed to bring down the local pain and improve joint function.[5,6]
O3 can be injected by peri-articular, intra-articular, or percutaneous means. It is considered a satisfactory treatment with a low risk of complications and high success rate.
APPLICATIONS OF OZONE
HERNIATED DISC
Herniated disc (back pain)
By entering the disc space through the hernia between the inner margin of the facet joints and the lateral nerve root under fluoroscopic control,access is gained into the pathologic disc space. Ozone brings about oxidation by proteoglycans thus reducing the osmotic pressure and bringing about shrinkage of the disc. The reduced osmotic pressure in turn improves the local blood circulation. Care should be taken to not to exceed the capacity of antioxidant enzymes and glutathione, as this would lead to a build up of superoxide anion and hydrogen peroxide which could in turn have adverse effects on the integrity of the cell membranes. [7]O3 is administered at a nontoxic concentration of 1 to 40 µg of O3 per milliliter of oxygen. The therapeutic effect is usually brought about by freeing of the nerve root owing to the shrinkage produced due to ozonolysis.
TEMPEROMANDIBULAR JOINT DYSFUNCTION
As this joint connects the jawbone to the skull, disorder of the temperomandibular joint(often found as a part of myofascial pain syndromes). Ozone therapy has been found to be more effective in significantly improving the pain scores and increasing the interincisal mouth opening values. Ozone is believed to stimulate fibroblastic activity which brings about joint repair when injected into the joint capsule. On splitting into separate oxygen atoms, O3 is able to react when in contact with a contaminant.[8,9,10]
A study has shown 87% of the patients treated with Ozone had marked improvement or complete resolution of symptoms.[10]
OSTEOARTHRITIS OF KNEE
Ozone infiltration into an arthritic knee accelerates anabolism leading to improved vascularisation of the cartilage and bone. Ozone also brings about inhibition of chondrocytes, stem cells, inflammatory cytokines, nitric oxide, and mineral metalloproteinases. It has also seen to improve the range of motion. Rout of administration can be intrarticular,periarticular or subcutaneous.
ADHESIVE CAPSULITIS OF THE SHOULDER
Ozone infiltration for the treatment of adhesive capsulitis/frozen shoulder can bring about reduction in both pain and inflammation. The mixture administered is generally 95-96% oxygen and about 4-5% of oxygen. Ozone destroys pain inducing/algogenic substances, regulates serotonin levels and also brings about inactivation of bradykinin. It also aids the physical therapy programme to regain the desired range of motion.
SHOULDER/GLENOHUMERAL ARTHRITIS
Ozone infiltration has shown to bring about marked improvement in the pain scores and also helps in improving the range of motion of the arthritic joint.
Patients with SUBACROMIAL BURSITIS and PARTIAL SUPRASCAPULARIS TEARS have also benefitted with image guided ozone interventions
HIP/TROCHANTERIC BURSITIS
Ozone given via a Pertrochanteric route for hip bursitis has seen to bring about reduction in inflammation, reduction in both daytime and night time pain as well as complete resolution of bursitis and the resulting limp in some patients.
RHEUMATOID ARTHRITIS
Studies have indicated that O3 can reduce the activity of TNF-α in the inflammatory tissues and suppress synovial hyperplasia and joint swelling in rheumatoid arthritis. This is often used along with Disease Modifying Anti Rheumatic drugs in the management of Rheumatoid Arthritis.
FIBROMYALGIA
Weekly or biweekly intravenous Ozone administration in fibromyalgia patients has shown to decrease pain, improve asthenia and bring about a general sense of well being. Duration and frequency of treatments are usually decided by the clinician depending on the response observed.
Other conditions where benefit has been seen with the use of Ozone are
- Carpal tummel syndrome
- Lumbar Facet Joint Syndrome
- Systemic sclerosis
- Cardoso CC, Carvalho JC, Ovando EC, Macedo SB, Dall’Aglio R, Ferreira LR. Action of ozonized water in preclinical inflammatory models. Pharmacol Res. 2000;42:51–54. [PubMed] [Google Scholar]
- Bocci V. Ozone as Janus: this controversial gas can be either toxic or medically useful. Mediators Inflamm. 2004;13:3–11. [PMC free article] [PubMed] [Google Scholar]
- Bocci V. Biological and clinical effects of ozone. Has ozone therapy a future in medicine? Br J Biomed Sci. 1999;56:270–279. [PubMed] [Google Scholar]
- Re L, Mawsouf MN, Menendez S, Leon OS, Sanchez GM, Hernandez F. Ozone therapy: clinical and basic evidence of its therapeutic potential. Arch Med Res. 2008;39:17–26. [PubMed] [Google Scholar]
- Lopes de Jesus CC, Dos Santos FC, de Jesus LMOB, Monteiro I, Sant’Ana MSSC, Trevisani VFM. Comparison between intra-articular ozone and placebo in the treatment of knee osteoarthritis: A randomized, double-blinded, placebo-controlled study. PLoS One. 2017;12:e0179185. [PMC free article] [PubMed] [Google Scholar]
- Cardelli R, de Santis F, Dall’Olio M, Leonardi M. Osteoarthritis of the hip treated by intra-articular infiltration of oxygen-ozone and hyaluronic acid (Hyalubrix®️). Preliminary results. Int J Ozone Ther. 2008;7:66–69. [Google Scholar]
- Bellomo G, Mirabelli F, Salis A, et al. Oxidative stress-induced plasma membrane blebbing and cytoskeletal alterations in normal and cancer cells. Ann N Y Acad Sci. 1988;551:128–130. [PubMed] [Google Scholar]
- Rahimi-Movaghar V, Eslami V. The major efficient mechanisms of ozone therapy are obtained in intradiscal procedures. Pain Physician. 2012;15:E1007–E1008. [PubMed] [Google Scholar]
- Bocci V, Zanardi I, Travagli V. Has oxygen-ozonetherapy a future in medicine. J Exp Integr Med. 2011;1:5–11. [Google Scholar]
- Daif E. Role of intra-articular ozone gas injection in the management of internal derangement of the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113:e10–e14. [PubMed] [Google Scholar]