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.