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

The neuropathic pain model consisting of the spared nerve injury of the sciatic nerve was used in the mouse to examin e wheth er peripheral neuropathy is capable of generating over-exp ression of pro-infl ammatory 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 af ter spared nerve injury of the sciatic nerve. Conversely, the expression of caspase-3 wa s decreased by spared nerve injury of the sciatic nerve in the same brain area. A single subcutaneous injectio n of ozone performed 12 h af ter 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-1 β 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-infl ammatory caspa ses and reduced IL-1 β staining in the orbito-frontal cortex astrocytes in SNI mice. These preliminary data show that periph eral neuropathy induced over-exp ression of pro-inflammatory/pro-apoptotic caspases in the orbi to-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 main tenance of allodynia.