title: Percutaneous Treatment of Herniated Lumbar Discs with Ozone: Investigation of the Mechanisms of Action.
abstract: OBJECTIVE
  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.
authors.affiliation: University of Toronto, Toronto, Ontario, Canada. Electronic address: Kieran.Murphy@uhn.on.ca.
authors.forename: Kieran
authors.initials: K
authors.lastname: Murphy
authors.affiliation: University of Toronto, Toronto, Ontario, Canada.
authors.forename: Gavin
authors.initials: G
authors.lastname: Elias
authors.affiliation: ActiveO Inc, Salt Lake City, Utah.
authors.forename: Jim
authors.initials: J
authors.lastname: Steppan
authors.affiliation: ActiveO Inc, Salt Lake City, Utah.
authors.forename: Chett
authors.initials: C
authors.lastname: Boxley
authors.affiliation: University of Utah, Salt Lake City, Utah.
authors.forename: Kuberan
authors.initials: K
authors.lastname: Balagurunathan
authors.affiliation: University of Utah, Salt Lake City, Utah.
authors.forename: Xylophone
authors.initials: X
authors.lastname: Victor
authors.affiliation: ActiveO Inc, Salt Lake City, Utah.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meaders
authors.affiliation: Antonio Cardarelli Hospital, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Muto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D016466:CHO Cells; D003198:Computer Simulation; D003412:Cricetulus; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D055119:Elastic Modulus; D006025:Glycosaminoglycans / Q000378:metabolism; D007278:Injections, Spinal; D007403:Intervertebral Disc / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007405:Intervertebral Disc Displacement / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008954:Models, Biological; D000070614:Nucleus Pulposus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009997:Osmotic Pressure; D010126:Ozone / Q000008:administration & dosage*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006025:Glycosaminoglycans; D010126:Ozone