Ozone Therapies
Ozone is Activated O2 that improves the immune system and helps to prevent and treat some diseases.
For acute pain, inflammation can arise from the damaged tissue and the immune responses to the damage. Whereas, for chronic pain, mitochondrial dysfunction could also involve pain neurons, signaling pathways, and the brain [4].
Many interventions that boost mitochondrial function, reduce inflammation, or improve blood flow can help relieve pain, especially chronic pain or injuries that don’t heal well. These interventions include low-level laser therapy, massages, transcutaneous electrical nerve stimulation, hyperbaric oxygen therapy, and exercise. Given that ozone therapy addresses these similar mechanisms, it’s a powerful adjunctive treatment that can provide relief. In addition, ozone therapy stimulates several regenerative pathways, so it also stimulates actual healing beyond just relief.
When administered, ozone interacts with biological tissues, leading to the formation of ozonides and other reactive oxygen species (ROS) which stimulate Nrf2 and other downstream processes. These ROS play a vital role in signaling pathways that promote mitochondrial activity [6]. At the same time, systemic ozone therapy and ozone-oxygen injections enhance tissue oxygenation and increase oxygen availability at the cellular level [7, 8].
The antioxidant pathway activation and oxygen stimulate the production of ATP for use inside the cells, improving cellular metabolism and reducing the accumulation of pro-inflammatory substances [9].
By enhancing mitochondrial function, ozone therapy not only aids in the repair of damaged tissues but also helps to modulate pain perception. Improved tissue oxygenation and mitochondrial activity can lead to faster healing, less inflammation, and thus less pain.
This mechanism makes ozone therapy particularly effective in treating conditions where chronic inflammation and low oxygen play a central role.
Routes of Ozone-Oxygen Administration for Pain
Local injection of gas into the joints or muscles
One of the most direct methods of administering ozone therapy for pain relief is the local injection of ozone gas into affected joints or muscles [23]. This provides targeted pain relief and promotes healing.
This approach allows the ozone to act directly on the site of pain to create a small amount of oxidative stress that jumpstarts the healing. At concentrations 20 - 40 μg/mL, it reduces inflammation, increases tissue oxygenation, and modulates nociceptor activity. Whereas, at higher concentrations, it may increase inflammation which may help fight infections [6].
Ozone injection or prolozone is particularly effective for conditions such as:
· Arthritis
· Tendonitis
· Musculoskeletal disorders
Ozone oil massage
Ozone oil massage involves the topical application of ozonated oil, which is oil infused with ozone, directly onto the skin over areas experiencing pain or inflammation [24]. It delivers fat-based molecules that ozone exposure creates. These molecules can penetrate the skin and deliver its anti-inflammatory and analgesic effects locally.
Ozone oil massage is particularly useful for treating surface-level pain conditions, such as:
· Muscle soreness
· Minor joint pain
· Skin-related inflammatory issues
Although this method has the least evidence for it, there is one triple-blind clinical trial in 80 severe osteoarthritis patients over 50 years old. The patients were instructed to apply 0.5 mL of oils topically on the affected joints and massage until complete absorption twice daily for 60 days. 37 patients received ozone oil massage while 43 received the placebo. The ozone oil group experienced statistically significant pain relief [25].
Systemic ozone treatment
Systemic ozone treatment involves administering ozone throughout the body to address widespread pain and inflammation. Two common methods are autohemotherapy (MAH) and rectal insufflation.
Both methods are used to:
· Reduce systemic inflammation
· Boost immune function
· Improve overall oxygenation, including to the brain
· Improve overall sense of wellbeing
These benefits make them effective for conditions characterized by chronic pain and widespread inflammation.
Case Studies and Research on Ozone Therapy for Musculoskeletal Disorders
Degenerative Disc Disease
In a case series published in Acta Neurochirurgica, Dr. Matteo Bonetti and his team of physicians used oxygen-ozone therapy for degenerative spine disease in elderly patients. Between April 2004 and March 2008, their team chose 129 patients who showed evidence of spondyloarthrosis and disc degeneration and who had contraindications preventing them from taking standard anti-inflammatory and analgesic drugs.
The treatment was CT-guided injections of 10 cc of ozone-oxygen gas mix at 25 µg/mL into each infiltration point.
At 3 months:
· 57.3% (74) of patients had near complete disappearance of low back pain
· 24.8% (32) were satisfied with the treatment but only had partial reduction of pain
· 17.9% (23) had little to no benefit
At 1 year follow up, 2 patients had passed. However, 33.9% (43/127) patients still had a clear-cut improvement in quality of life as their pain had resolved and they were able to return to daily activities. Ten of these patients no longer required walking aids. The pain came back for 34 patients with partial resolution of pain, but the recurred pain was much milder than before the ozone-oxygen treatment. Only 1 patient in this study chose surgical decompression.
The study concluded that ozone therapy was an ideal treatment with no side effects in elderly patients with degenerative spine disease [27].
Herniated Discs
Herniated discs are a common injury for athletes and there’s an increased risk of them occurring with age. The condition occurs when a tear in the fibrous ring of an intervertebral disc allows the central portion to bulge out, leading to significant pain, discomfort, and hindered mobility. There are few treatment options other than pain management, physical therapy, and surgery. Fortunately, ozone therapy is a very safe, effective, and minimally invasive option.
A 2024 meta-analysis evaluated the effectiveness of ozone injections for lumbar disc herniations. It reported that at ≥ 6 months, the therapeutic was 3.95 times more likely to give superior outcome to steroid injections or conventional medications.
· < 6 months the reduction in VAS after injection was 2.53 points higher than after steroid injections.
· At 6 months, change in VAS was 1.65 points
· At 12 months, 1.52 points
This meta-analysis concluded that ozone injections were more effective than steroids and other oral medications [29].
On average, the pain levels improved by 3.77 out of 10 on the VAS scale. JOA improved by 54.7% and OPRS improved by 71.55%. With respect to imaging, 37% of patients had complete disappearance of the herniation, while 41% had a reduction in volume, and 22% had unchanged herniation [31].
Sciatica
Since many musculoskeletal issues that originate or branch off of the spine work in similar ways (such as inflammation or muscle and tissue tears creating pinched nerves and nerve pain), ozone therapy provides similar benefits for many of them, including sciatica and lower back pain more generally.
In a study published in La Radiologica Medica, researchers treated more than 1000 patients with intradiscal ozone for lower lumbar and sciatic pain while they were under anesthesia between September 1995 and April 1997. Of those patients, researchers selected 50 for these treatments at intervals of three, 15, and 30 days, with follow-ups after each one and a final follow-up three months later.
The study’s results showed 68% positive results, meaning those patients didn’t need surgery or other medical and/or pharmaceutical care. In the conclusion of their study, the care team were optimistic about the use of ozone therapy as an early intervention for sciatica and back pain:
Ozone therapy, thanks to its ease of execution and noninvasiveness, permits the successful outpatient treatment of lumbar sciatic pain. Moreover, the lack of major complications and the good results obtained compared to other methods, such as chemonucleolysis, percutaneous automated discectomy, microsurgery and conventional surgery, suggest that ozone therapy can be considered the treatment of choice for lumbar sciatic pain and a valid alternative to surgery in many cases [34].
Tendonitis
Tendonitis can affect many different joints in the body, and most cases tend to come from excess physical strain on a certain part of the body. Tendons and ligaments tend to heal very slowly as they naturally have low blood supply. Also, autoimmune issues, mold toxicity, and other musculoskeletal issues can also cause or exacerbate these problems.
A clinical study looked at rotator cuff injuries in 40 patients, 26 men and 14 women, who had been experiencing shoulder pain for approximately six months. According to the researchers, "ultrasound-guided infiltration of oxygen-O3 therapy proved to be an effective treatment method in partial tears of the supraspinatus tendon” [30].
Carpal Tunnel Syndrome
A case study by Zambello et al. showed that 90% of carpal tunnel patients had "significant improvement” after getting injections of ozone therapy. After a year, 17% noted that they had good control over their symptoms and 70% noted that they no longer experienced any symptoms [37].
The study concluded that ozone therapy provided more significant long-term pain relief, improved hand function, and enhanced median nerve conduction over six months than steroids [38].
Fibromyalgia
A randomized controlled trial aimed to evaluate the effectiveness of ozone therapy (OT) as an additional treatment for fibromyalgia (FM), a chronic condition characterized by widespread pain, fatigue, and sleep disturbances [39].
54 patients were divided into an OT group and a placebo control (PC) group. Participants received ozone therapy or placebo in the form of major autohemotherapy (MaAHT) and minor autohemotherapy (MiAHT) twice a week for a total of 10 sessions.
The treatment’s effectiveness was assessed using the Fibromyalgia Impact Questionnaire (FIQ), Pittsburgh Sleep Quality Index (PSQI), and 12-item Short-Form Health Survey (SF-12) before and after the intervention.
The results showed that the OT group experienced significant (p < 0.05):
· Improvements in specific FIQ subscales, such as feeling good and fatigue
· PSQI total score and subscales, including subjective sleep quality, sleep latency, and sleep disturbances.
Ozone therapy, particularly when applied via autohemotherapy, can improve specific aspects of fibromyalgia symptoms and sleep quality during the treatment period.
Peripheral neuropathy
There are numerous causes of neuropathy, from metabolic issues to infections, autoimmune disease, toxic exposures, metabolic issues, hormone imbalances, genetics, physical traumas, and more. Ozone therapy may be more effective for certain causes of neuropathy than others.
An RCT evaluated the efficacy of combining pulsed radiofrequency therapy with ozone injection for treating acute herpes zoster neuralgia (shingles pain) in 164 middle-aged and elderly adults [40].
The treatments’ effectiveness was assessed using Numeric Rating Scale (NRS) scores. The incidence of clinically significant prolonged nerve pain after the shingles had resolved and any complications were also recorded.
Results demonstrated significant (p < 0.05):
· Reductions in NRS scores and gabapentin doses post-treatment compared to baseline
· Lower doses of gabapentin postoperatively
· Reduction in prolonged nerve pain incidences at 4, 12, and 24 weeks post-treatment
No adverse reactions were reported in either group.
Combination therapy provides longer-lasting pain relief, reduces the incidence of PHN, lowers the need for medication, and improves the quality of life.
Complex Regional Pain Syndrome
A case report discussed the potential of ozone therapy as a novel approach for treating pain, specifically focusing on Complex Regional Pain Syndrome (CRPS), also known as Reflex Sympathetic Dystrophy (RSD) [42].
CRPS is a multifaceted and painful disorder that is difficult to manage with conventional treatments. The report highlights ozone therapy's unique mechanisms of action, which include oxygenation, immune modulation, anti-infective, and anti-inflammatory. All of these may address the underlying factors contributing to CRPS and other chronic pain conditions.
The case presented involves an 11-year-old girl diagnosed with CRPS and frequent pseudoseizures, who had not responded to traditional pain management, including opioids. She was treated with direct intravenous ozone therapy nearly daily, resulting in rapid improvement. After 120 sessions, all symptoms of CRPS and pseudoseizures had disappeared.
Knee Osteoarthritis
According to a 2024 umbrella review of systematic reviews, thAn RCT evaluated the therapeutic effects of combining ozone with articular injection of sodium hyaluronate on 292 patients with knee osteoarthritis (KOA) to assess changes in their inflammatory factors and hemorheological indices [43].
The ozone group (n=146) received ozone therapy combined with sodium hyaluronate injections. The control group (n=146) was treated with oral glucosamine hydrochloride tablets and sodium hyaluronate injections. The treatment was administered once a week for five consecutive weeks.
The results showed that the ozone group experienced significantly (p < 0.05):
· Lower Visual Analogue Scale (VAS) scores for pain
· Higher knee function based on the Hospital for Special Surgery (HSS) knee scores
· Total response rate to treatment
· Lower levels of inflammatory factors in the joint fluid
· 15 randomized controlled trials in 6 countries that evaluated the safety and effectiveness of ozone injections for knee osteoarthritis. Three of these trials reported that ozone injections provided better pain reduction than placebo, but may not be superior to other treatments [44].
The study concludes that ozone combined with articular injection of sodium hyaluronate offers significant therapeutic benefits for patients with KOA, providing:
· Better pain relief
· Improved knee function
· A reduction in inflammatory factors
Conclusion
Though ozone therapy is not a cure for these diseases, ongoing research shows that it may help provide relief and often resolve the issues. Most importantly, it serves as an intermediary treatment option between very invasive treatment options like surgery and more surface-level options like physical therapy for those who need it the most. For several conditions like lumbar back herniations and osteoarthritis, there is ample evidence confirming the safety and effectiveness of ozone therapy.
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