Ozone therapy: Help for acute and chronic pain management

Ozone therapy is used for its antioxidant, anti-inflammatory and analgesic properties. Its clinical history dates back to 1902, where it was shown to treat middle ear infections¹ and other infections during the first world war. Since then, many clinical studies have emerged proving its safety and efficacy for acute and chronic infections, fatigue, autoimmune conditions, cardiovascular disease, cancer and pain.

Ozone (O3) is a reactive molecule that is generated when oxygen (O2) is exposed to high energy, splits, and recombines into O3. It exists naturally in the earth’s atmosphere to protect us from harmful UV radiation and is formed during lightning storms. Do you remember the smell of a thunderstorm? That’s ozone! 

This high energy molecule can be recreated in a clinical setting with the use of ozone generators. Ozone can be delivered depending on the need, whether as injections to relieve pain locally or as major autohemotherapy to target the body systemically. The purpose of this article is to review the use of intra-articular ozone injections for its analgesic and anti-inflammatory properties. The mechanisms of action, clinical indications and what to expect from treatment is outlined below. 

Mechanism of action
Ozone gas is a reactive molecule that induces a mild and transient oxidative stress response. The gas quickly reacts with organic double bonds^4,2 (lipids and amino acids) and aqueous solutions (interstitial fluid, plasma and lymph). This initiates a cascade of biologically active substrates and anti-oxidant enzymes,³ resulting in lowered oxidative stress.⁴ These effects help to reverse the damage caused by infection, chronic inflammation and a lack of sufficient oxygen (hypoxia). 

A review of mechanisms that cause pain:

• Hypoxia impairs cellular mechanisms involved in repair and mitochondrial energy production. The resulting increase in reactive oxygen species (ROS), acidosis and oxidative stress generates pain.⁵
• Inflammatory mediators such as tumor necrosis factor (TNF) are also involved in the generation and maintenance of pain.⁶

Due to their anatomical location, joints and ligaments receive poor circulation, making them vulnerable to hypoxia and reduced nutrient delivery. Any trauma to these areas causes a cycle of local inflammation further diminishing circulation, increasing local acidosis and free radical production.⁷

Ozone intra-articular injection therapy breaks these cycles of pain generation^4,8

• Improves circulation and oxygen utilization through oxygen-hemoglobin dissociation and mitochondrial metabolism.⁷
• Decreases inflammation and oxidative damage. Ozone therapy has been shown to reduce inflammatory cytokines such as TNF- and active anti-inflammatory mediators such as IL-10.⁹ TNF- is a known proinflammatory cytokine and has been linked with joint pain and increased oxidative joint damage. 
• Direct antimicrobial action for any existing local infection. Ozone directly disrupts microbial cell walls (fungi and bacteria) and prevents of virus-to-cell contact.

Conditions that benefit from ozone injection therapy

• Myofascial pain syndrome⁵
• Osteoarthritis¹⁰
• Lumbar disc herniation and sciatica^11,12
• Rheumatoid arthritis¹
• Plantar fasciitis¹³
• Carpal tunnel syndrome¹⁴

Joint instability including those with Ehlers Danlos, a connective tissue disorder that often presents with ligament laxity, frequent joint subluxations and pain

What to expect from the therapy
Ozone injections are initiated after a comprehensive assessment of the pain and any pertinent orthopedic tests. The injections themselves cause very little discomfort (other than some pressure or tenderness as the gas is injected into the area). 

There is often an immediate response with most experiencing improvement in stability and pain of the area. Patients are encouraged to stop any aggravating activities after the treatment to allow the area to heal, but continue gentle range of motion. Long term responses differ for each case and can take 3-5 treatments with some requiring maintenance ‘booster’s’ every 3-4 months.

In summary, ozone is an effective clinical tool that has a wide variety of uses with minimal side effects. Its effectiveness and safety has been shown in recent literature for the its ability to reduce pain and chronic oxidative stress for a number of acute and chronic conditions. 

References

1. Stoker G. (1902). Ozone in Chronic Middle-Ear Deafness. The Lancet. 160(4131):1187-1188.
2. Bocci, V., Borrelli, E., Zanardi, I., & Travagli, V. (2015). The usefulness of ozone treatment in spinal pain. Drug design, development and therapy, 9, 2677–2685. https://doi.org/10.2147/DDDT.S74518
3. Shallenberger, F. (2011). Prolozone™ – Regenerating Joints and Eliminating Pain. Journal of Prolotherapy
4. Smith, N. L. et al. (2017). Ozone therapy: an overview of pharmacodynamics, current research, and clinical utility. Medical gas research, 7(3), 212–219. https://doi.org/10.4103/2045-9912.215752
5. Tony, K. Y. et al. (2015). Mitochondrial and Bioenergetic Dysfunction in Trauma-Induced Painful Peripheral Neuropathy. Molecular Pain. 11.
6. Leung, L., & Cahill, C. M. (2010). TNF-alpha and neuropathic pain–a review. Journal of neuroinflammation, 7, 27. https://doi.org/10.1186/1742-2094-7-27
7. Shallenberger, F. (2011). Principles and Applications of Ozone Therapy. A Practical Guide for Physicians
8. Raeissadat, S. A. et al. (2018). Comparison of ozone and lidocaine injection efficacy vs dry needling in myofascial pain syndrome patients. Journal of pain research, 11, 1273–1279. https://doi.org/10.2147/JPR.S164629
9. Tartari, A.P.S., Moreira, F.F., Pereira, M.C.D.S. et al. (2020). Anti-inflammatory Effect of Ozone Therapy in an Experimental Model of Rheumatoid Arthritis. Inflammation 43, 985–993.
10. Al-Jaziri, A. A., & Mahmoodi, S. M. (2008). Painkilling effect of ozone-oxygen injection on spine and joint osteoarthritis. Saudi medical journal, 29(4), 553–557.
11. Paoloni, M. et al. (2009). Intramuscular oxygen-ozone therapy in the treatment of acute back pain with lumbar disc herniation: a multicenter, randomized, double-blind, clinical trial of active and simulated lumbar paravertebral injection. Spine, 34(13), 1337–1344. https://doi.org/10.1097/BRS.0b013e3181a3c18d
12. Bonetti M, et al.(2005).. Am J Neuroradiol. 26(5):996-1000.
13.  Bahrami, M. H. et al. (2019). Local ozone (O2-O3) versus corticosteroid injection efficacy in plantar fasciitis treatment: a double-blinded RCT. Journal of pain research, 12, 2251–2259. https://doi.org/10.2147/JPR.S202045
14. Seyam, O., Smith, N. L., Reid, I., Gandhi, J., Jiang, W., & Khan, S. A. (2018). Clinical utility of ozone therapy for musculoskeletal disorders. Medical gas research, 8(3), 103–110. https://doi.org/10.4103/2045-9912.241075

DR. WHITNEY BAXTER, ND, CEP (ACSM) Prior to becoming a naturopathic doctor, she worked as an exercise physiologist in cardiac rehab. It was here that she witnessed the value of a holistic approach to health care and understood that each individual’s physical, mental, and emotional health are interconnected. She has a general practice and enjoys working with mental wellness, digestive health and cardiovascular disease management and prevention.