How Do Ozone Therapy Injections Work?
Today I’m going to start writing about a bit of a different topic from my prior posts: injections. Injections are gaining popularity in healthcare, and you can find a practitioner in just about every city who is willing to perform any number of different types – cortisone, PRP, ozone, stem cells – the list keeps growing. They are becoming increasingly popular for treating a host of different problems, from stubborn pain to injuries that providers have all but given up on trying to treat. However, a lot of providers, myself included, are guilty of telling patients about these options while having no idea how each type of injection works or how to treat them. This can be frustrating and detrimental for patients, since they have to pay for the majority of these treatments out of pocket. I’m here to change that.
This is the first post in a series that will focus on what exactly these different injections are, how they work, and when each might be the most appropriate. Today we will look at a brief history of ozone therapy and its mechanisms of action. In particular, the majority of research on using ozone for musculoskeletal-related pain has focused on knee osteoarthritis, so that is what I will be specifically covering today. (Note: these posts will be a lot more technical than most. For a concise overview of how it works without all the technical details, skip to the summary.)
Ozone Therapy History
Ozone, or O3, is an atmospheric gas that rapidly decomposes to oxygen. It is an excellent example of a compound with hormetic properties, meaning that it has beneficial effects in low doses and detrimental effects in large doses. Ozone therapy first appeared in the 1800s, with the first medical ozone generator patent going to the one and only, Nikola Tesla (no car or stock included). It gained traction during WWI, when it was used as a topical disinfectant for soldiers’ wounds, but it fell out of favor after the war until the 1980s and 90s, when it began to gain steam again as a treatment for HIV (it turned out to not be as effective as anticipated). Ozone therapy has remained a relatively well-known treatment since then, with the first large-scale look at ozone injections into joints beginning in the 2010s.
Ozone Therapy Mechanisms of Action
Increased Antioxidant Capacity
Ozone therapy via injection works through a few different pathways. The first is by increasing antioxidant capacity… albeit counter-intuitively. When ozone is injected, it reacts with polyunsaturated fatty acids and water, creating hydrogen peroxide and a mixture of lipid ozonation products (think oxidation, and therefore reactive oxidation species, or free radicals).
At first glance, this seems harmful, because the introduction of ozone increases the agents of inflammation. However, this increase in oxidative stress leads to the activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway, which activates the transcription of antioxidant response elements (AREs); Nrf2 is part of a larger signaling pathway that regulates anti-inflammatory gene expression and may be responsible for many of the effects seen with systemic ozone therapy use. These AREs then increase the antioxidant enzyme concentration, which act as free radical scavengers. In addition, these inflammatory molecules induce the proliferation of chondrocytes and fibroblasts (cells that produce cartilage and collagen, respectively), both of which are helpful to have when combatting a condition that destroys cartilage and connective tissue.
Another way of looking at what is happening here is to think of the administration of ozone as preconditioning the local tissues to oxidative stress. By producing acute oxidative stress, ozone increases the concentration of antioxidants in that area, which then results in a protective state against further tissue damage. This is important if you are looking to create an environment where healing can occur without causing excess stress to the tissues that would restart the inflammatory process.
Increased Oxygen Availability
A second mechanism of action for ozone therapy is via changes in oxygen levels at the cellular level. There are two mains components here: first, the injection of ozone increases the levels of O2 in the cells surrounding the injection site due to an increased concentration of O2 outside the cells. This change makes mitochondrial respiration more efficient; when the efficiency of mitochondrial respiration improves, the production of free radicals decreases, which leads to an overall decrease in inflammation in the affected cells and surrounding tissue. Another benefit of the presence of increased oxygen is that the oxyhemoglobin dissociation curve is shifted to the right; what this means is oxygen molecules that are bound to hemoglobin can be unloaded more easily into tissues with impaired blood flow. Both of these effects are important when dealing with osteoarthritis, since impaired blood flow (ischemia) and vascular deficiencies are often seen in these patients and may even be a causative factor. Similarly, blood flow changes to the ischemic tissues are also changed due to dilation of the blood vessels (vasodilation) and an increase in the total number of blood vessels (angiogenesis), which are induced by the initial inflammatory effects of the ozone therapy.
Summary
Two of the primary mechanisms by which ozone therapy injections work are by decreasing inflammation and increasing oxygen availability to ischemic cells. While ozone is an inflammatory molecule, the initial inflammation that it instigates is counteracted by the body, to a greater degree than the inflammation, which then preconditions the body against further inflammatory stress (it’s like calling Lebron James off the bench in your 3v3 pickup game because the other team went up 4-0; by the time you pull him out, your point cushion will be insurmountable).
In addition, ozone therapy increases the availability of oxygen to the damaged tissues by inducing blood flow changes, changing the concentration of O2 in the nearby cells, and making it easier for oxygen to dissociate from hemoglobin in the injured tissues.
I hope this provides a helpful overview for you on the history and mechanisms behind the use of intra-articular ozone injections. If you are considering trying injections before some type of surgery and want to learn more, or if you are thinking about giving physical therapy a shot, click the link below to schedule a free consultation!
The majority of this blog came from a post I made for another blog, Century of Performance. To read more content that is similar to this post, you can visit centuryofperformance.com.
Western Slope Rehab and Performance is Here to Help
If you are struggling with injuries or have recently been in a motor vehicle accident, we can help. We are a physical therapy company that provides home-based orthopedic services in the Grand Junction, CO, area, as well as telehealth appointments throughout Colorado. If you would like to schedule a free consultation, you can call us as 970-462-9177, or fill out our contact form here.
If you found this post valuable, please like and share on our Facebook page, which is updated regularly with new content.