Percutaneous Treatment of Herniated Lumbar Discs with Ozone: Investigation of the Mechanisms of Action

J Vasc Interv Radiol. 2016 Aug;27(8):1242-1250.e3. doi: 10.1016/j.jvir.2016.04.012. Epub 2016 Jun 28.


Purpose: To elucidate the mechanism of action of intradiscal oxygen-ozone therapy for herniated intervertebral disc therapy.

Methods: Ozone's mechanism of action was investigated using 3 approaches: mathematical models of intervertebral disc space to explore the relationship between disc pressure and volume; ozonolysis experiments using glycosaminoglycans (GAGs) from a Chinese hamster ovary cell line that were similar in composition to GAGs found in human nucleus pulposus; and experiments in which live Yucatan miniature pigs received various concentrations of percutaneous, image-guided intradiscal oxygen-ozone treatment and were examined (after sacrifice) with histology and semiquantitative analysis of disc cytokine concentrations.

Results: Engineering calculations support observations that a small (6%) disc volume reduction can result in considerable (9.84%) intradiscal pressure reduction. Porcine disc histology and Chinese hamster ovary GAG ozonolysis results showed that administered ozone reacted with and fragmented disc proteoglycans, reducing disc volume through disc dehydration. Cytokine analysis of porcine discs found that each of 4 cytokines measured (interleukin [IL]-1β, IL-6, IL-8, and tumor necrosis factor α) increased in concentration after 2 wt% ozone treatment.

Conclusions: Oxygen-ozone therapy breaks down proteoglycan GAGs that maintain disc osmotic pressure, dehydrating the nucleus pulposus and reducing intervertebral disc volume. This is likely a primary mechanism by which ozone relieves nerve root compression and alleviates herniated disc-related pain. Additionally, 2 wt% ozone appears to interact with intradiscal cytokines, generating an antiinflammatory response that may contribute to symptom improvement.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • CHO Cells
  • Computer Simulation
  • Cricetulus
  • Cytokines / metabolism
  • Disease Models, Animal
  • Elastic Modulus
  • Glycosaminoglycans / metabolism
  • Injections, Spinal
  • Intervertebral Disc / drug effects*
  • Intervertebral Disc / metabolism
  • Intervertebral Disc / pathology
  • Intervertebral Disc / physiopathology
  • Intervertebral Disc Displacement / drug therapy*
  • Intervertebral Disc Displacement / metabolism
  • Intervertebral Disc Displacement / pathology
  • Intervertebral Disc Displacement / physiopathology
  • Lumbar Vertebrae / drug effects*
  • Lumbar Vertebrae / metabolism
  • Lumbar Vertebrae / pathology
  • Lumbar Vertebrae / physiopathology
  • Models, Biological
  • Nucleus Pulposus / drug effects
  • Nucleus Pulposus / metabolism
  • Nucleus Pulposus / pathology
  • Osmotic Pressure
  • Ozone / administration & dosage*
  • Swine
  • Swine, Miniature


  • Anti-Inflammatory Agents
  • Cytokines
  • Glycosaminoglycans
  • Ozone