A single subcutaneous injection of ozone prevents allodynia and decreases the over-expression of pro-inflammatory caspases in the orbito-frontal cortex of neuropathic mice

Eur J Pharmacol. 2009 Jan 28;603(1-3):42-9. doi: 10.1016/j.ejphar.2008.11.060. Epub 2008 Dec 6.


The neuropathic pain model consisting of the spared nerve injury of the sciatic nerve was used in the mouse to examine whether peripheral neuropathy is capable of generating over-expression of pro-inflammatory and pro-apoptotic genes in the orbito-frontal cortex, together with allodynia and hyperalgesia. RT-PCR analysis showed increased expression of caspase-1, caspase-12 and caspase-8 genes in the orbito-frontal cortex 14 days after spared nerve injury of the sciatic nerve. Conversely, the expression of caspase-3 was decreased by spared nerve injury of the sciatic nerve in the same brain area. A single subcutaneous injection of ozone performed 12 h after the surgical procedure decreased mechanical allodynia and normalized the mRNA caspase-1, caspase-12 and caspase-8 gene levels, but did not the decrease caspase-3 level, 14 days post-spared nerve injury. Ozone also reduced IL-1beta staining in the orbito-frontal cortex in neuropathic mice. This study provides evidence that a single subcutaneous administration of ozone decreased neuropathic pain type behaviour, normalized the expression of pro-inflammatory caspases and reduced IL-1beta staining in the orbito-frontal cortex astrocytes in SNI mice. These preliminary data show that peripheral neuropathy induced over-expression of pro-inflammatory/pro-apoptotic caspases in the orbito-frontal cortex and that ozone, by mechanisms that are as yet unknown, can regulate the expression of the genes that play a pivotal role in the onset and maintenance of allodynia.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Astrocytes / drug effects
  • Astrocytes / immunology
  • Behavior, Animal / drug effects
  • Caspases / genetics*
  • Frontal Lobe / drug effects*
  • Frontal Lobe / enzymology
  • Frontal Lobe / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Hyperalgesia / drug therapy
  • Inflammation / enzymology
  • Inflammation / genetics
  • Injections, Subcutaneous
  • Interleukin-1beta / immunology
  • Male
  • Mice
  • Ozone / administration & dosage*
  • Ozone / pharmacology*
  • Ozone / therapeutic use
  • Pain / metabolism
  • Pain / prevention & control*
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / enzymology
  • Peripheral Nervous System Diseases / genetics*
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism


  • Interleukin-1beta
  • Ozone
  • Caspases