Ozone therapy has been used to treat disc herniation for more than four decades. There are several papers describing results and mechanism of action. However, it is very important to define the characteristics of extruded disc herniation. Although ozone therapy showed excellent results in the majority of spinal diseases, it is not yet fully accepted within the medical community. Perhaps it is partly due to the fact that, sometimes, indications are not appropriately made. The objective of our work is to explain the mechanisms of action of ozone therapy on the extruded disc herniation. Indeed, these mechanisms are quite different from those exerted by ozone on the protruded disc herniation and on the degenerative disc disease because the inflammatory response is very different between the various cases. Extruded disc herniation occurs when the nucleus squeezes through a weakness or tear in the annulus. Host immune system considers the nucleus material to be a foreign invader, which triggers an immune response and inflammation. We think ozone therapy modulates this immune response, activating macrophages, which produce phagocytosis of extruded nucleus pulposus. Ozone would also facilitate the passage from the M1 to M2 phase of macrophages, going from an inflammatory phase to a reparative phase. Further studies are needed to verify the switch of macrophages.

PURPOSE: Show light on the biological mechanism of ozone in DDD. The increase in life expectancy in the population brings to the increase of diseases associated with aging: cancer, heart disease, diabetes and low back pain. DDD and osteoarthritis are the most common causes of chronic joint-related disability and disabling pain in adults. Aging of the organism is the result of accumulation of molecular and cellular alterations over time, leading to a physiological and functional decrease of tissues. ANALYSIS AND DISCUSSION: In the Intervertebral discs (IVDs), aging can be schematized in 3 phases: accumulation of damaged bio-molecules, aberrant cellular response to the lesion and loss of structure and biological function. This perspective focuses on considering that the aging mechanisms are senescence, inflammation and oxidative damage. The IVDs acquire fissures and neo-vascularisation, this causes that the resident cells that are accustomed to the low voltage of oxygen, are exposed to a greater tension of oxygen and therefore to the oxidative stress. During aging, IVD cells change from the anabolic to catabolic phenotype. There is increased necrosis, apoptosis, and cell senescence. The NF-kB signal is central in the inflammatory response, stress and injury. There is a chronic activation of NF-kb correlated with oxidative stress and degeneration. Symptomatic discs have high levels of pro-inflammatory cytokines that are considered targets of NF-kB. CONCLUSION: For many years attempts have been made to inhibit the action of NF-kb and other inflammatory targets to mitigate DDD without favourable results. However, ozone is the solution to this problem because it interferes precisely at the level of NF-kB avoiding its chronic activation. That is why, in DDD there are sustainable improvements on patients, despite the fact that the MRI images show no significant changes.

INTRODUCTION: Ozone is the best available therapeutic resource for disc herniation, but once the pain is resolved, the intervertebral disc is left with a scar as well as volume reduction, and therefore to osteoarthritis. This situation affects all the anatomical structures that are part of the intervertebral space. This is why Degenerative Disc Disease (DDD) is currently considered a disease that affects not only the intervertebral disc but also the end plates and vertebral bodies. Several years ago we began studying therapeutics for DDD. It is our challenge, to prove that the intervertebral space regains its original integrity and homeostasis. In 2010 we developed an experimental model of regeneration of the intervertebral disc with mice, and the research protocol. Today, after overcoming some legal issues in Argentina, we begun the regeneration of the intervertebral disc in humans. PURPOSE: In this paper we present the firsts patients treated with ozone therapy and pre-differentiated cartilage cells, from February 2016 to the present. MATERIALS AND METHODS: Patients with DDD who meet the inclusion and exclusion criteria. Subcutaneous cellular tissue and blood were extracted, which were processed according to the corresponding technique to obtain pre-differentiated cartilage cells. After 21 days, the cells were implanted back to the patient in the operating room under neuroleptoanesthesia and radioscopic control. During these days an oxidative preconditioning with ozone was realized to modulate the microenvironment. RESULTS: Patients showed significant improvement in their pain and RMN images by comparing VAS scales before and after treatment. DISCUSSION: The combination of pre-differentiated cartilage cells with ozone therapy is an effective, novel and minimally invasive treatment for DDD. We must increase the number of cases in order to strengthen our results.