Ozone: Is it a better option to treat pain in Covid era?
The world is now facing one the biggest crisis known to mankind, the Coronavirus pandemic. This COVID-19 is multiplying at an unprecedented pace, affecting population worldwide. Coronaviruses have abundant cysteine in their spike proteins. It has been studied that the cysteine residues are also present in viral membrane proteins and must be “conserved” for viral cell entry.1
Ozone is a molecule consisting of three atoms of oxygen in a dynamically unstable structure2,3,4. Ozone gas has been used in pain medicine practice for intra articular injections, intradiscal, periforaminal or intraforaminal injections. Ozone is inherently bacteriostatic, fungicidal, and virucidal. Coronavirus structure has it’s spike and envelope proteins rich in cysteine, similar to Ebola virus. Ozone has a unique ability to inactivate cysteine dependent proteins.
Blood when treated with ozone immediately reacts with electron-rich double bonds of lipids and other molecules leading to formation of weak oxidant metabolites called ozonides.1 Ozonides act as messengers for the key biochemical and immune modulating effects of the therapy. The Menendez Cuban group found that preconditioning animals with ozone is as powerful as dexamethasone in reducing tumor necrosis factor α in subsequent endotoxic shock 5. This could be key in solving the problem of “cytokine storm”, that occurs due to pulmonary infection in coronavirus affected individuals.6,7,8
Ozone has been used for intra articular knee injections in mild to moderate osteoarthritis. Ozone when utilised as an intra-articular injection has been seen to decrease pain along with immunomodulatory effects on cartilage and reduction of oxidative stress.9 Ozone due to it’s highly reactive nature, stimulates fibroblastic joint repair, reduces inflammation and promotes new cartilage growth when injected inside a joint.10
Intradiscal injection of ozone gas has been used as an alternative to epidural steroids and surgical discectomy. Ozone is a strong oxidizer and its application to the nucleus results in cleaving of the proteoglycan molecules and neutralization of the negatively charged sulfate side chains.11 This likely reduces the disc’s ability to retain water and results in a reduction of the herniation volume.12
In the current situation due to the Coronavirus pandemic, we as pain physicians need to be very judicious while doing the various pain interventions. It becomes all the more important that we use the right agent during the injections.
Platelet-rich plasma injections are utilised as a regenerative treatment option for osteoarthritis, tendinopathies, partial tears of ligament or tendons etc. The process of withdrawing blood, separation of the platelets would definitely pose a risk to both the patient and the practitioner. The proximity to the patient required is also more during taking the blood sample and for injecting the platelet-rich plasma into the desired location. Interventional procedures involving the administration of platelet-rich plasma carry a very high risk of injecting viremic plasma.13
Pain physicians worldwide use corticosteroids injections commonly for spine interventions, inflammatory arthritis affecting joints, tendons etc. In the current pandemic crisis the one complication that cannot be overlooked is that of reduction in immune response caused by these injections. This would again amplify the risk of contracting the corona virus infection. Hence a risk-and-benefit ratio should be weighed, specifically the corticosteroid dosage, if they need to be administered keeping in mind the risk of immunosuppression.13
The world is being crippled by the Coronavirus pandemic. As health care professionals the best way to protect ourselves against it is by using the personal protective measures and following the safety recommendations and guidelines. In the present COVID-19 scenario, as pain specialists our hands are tied as to which injectable agent to use for different interventions. Ozone therapy has been proven to be safe with encouraging effects in pain control and functional recovery. Hence, in the present situation Ozone seems to be a better alternative to steroid or platelet-rich plasma injections.
- Rowen RJ, Robins H (2020) A Plausible “Penny” Costing Effective Treatment for Corona Virus- Ozone Therapy. J Infect Dis Epidemiol 6:113. doi.org/10.23937/2474-3658/1510113
- Di Paolo N, Bocci V, Gaggioti E. Ozone therapy editorial review. Int J Artifi cial Organs 2004;27:168-75.
- Bocci V. Biological and clinical eff ects of ozone: Has ozone therapy a future in medicine? Br J Biomed Sci 1999;56:270-9.
- Bocci V. Does ozone therapy normalize the cellular redox balance? Implications for the therapy of human immunodeficiency virus infection and several other diseases. Med Hypothesis 1996;46:150-4.
- Zamora A, Borrego A, Lopez O, Delgado R, Gonzalez R,et al. (2005) Effects of ozone oxidative preconditioning on TNF-α release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock. Mediators Inflamm 2005: 16-22.
- Liu Q, Zhou YH, Yang ZQ (2016) The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol 13: 3-10.
- Tetro JA (2020) Is COVID-19 receiving ADE from other coronaviruses? Microbes Infect. 22: 72-73.
- Huang C, Wang Y, Li X, Ren L, Zhao J, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497-506.
- Fernandez-Cuadros ME, Perez-Moro OS, Albaladejo-Florin MJ, Algarra-Lopez R. Ozone decreases biomarkers of inflammation (c-reactive protein and erythrocyte sedimentation rate) and improves pain, function and quality of life in knee osteoarthritis patients: A before and- after study and review of the literature. Middle East Rehabil Heal 2018.
- Fernandez-Cuadros ME, Perez-Moro OS,Mirón-Canelo JA.Could ozone be used as a feasible future treatment in osteoarthritis of the knee? Divers Equal Heal Care 2016 ; 13:232-239.
- Soltes L, Mendichi R, Kogan G, Schiller J, Stankovska M, Arnhold J. Degradative Action of Reactive Oxygen Species on Hyaluronan. Biomacromolecules. 2006;7:659–668. [PubMed] [Google Scholar]
- Lenhert T, Naguib NN, Wutzler S, Nour-Eldin NE, Bauer RW, Kerl JM, et al. Analysis of disk volume before and after CT-guided intradiscal and periganglionic ozone-oxygen injection for the treatment of lumbar disc herniation. J Vasc Interv Radiol. 2012;23(11):1430–1436. [PubMed] [Google Scholar]
- Tople JP, Das G. COVID-19 and Interventional Pain Practice. J Recent Adv Pain 2020;6(1):1–3.