title: 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.
abstract: 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.
authors.affiliation: Department of Experimental Medicine, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Fuccio
authors.forename: Carlo
authors.initials: C
authors.lastname: Luongo
authors.forename: Paola
authors.initials: P
authors.lastname: Capodanno
authors.forename: Catia
authors.initials: C
authors.lastname: Giordano
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Scafuro
authors.forename: Dario
authors.initials: D
authors.lastname: Siniscalco
authors.forename: Biagio
authors.initials: B
authors.lastname: Lettieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Rossi
authors.forename: Sabatino
authors.initials: S
authors.lastname: Maione
authors.forename: Liberato
authors.initials: L
authors.lastname: Berrino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology; D001522:Behavior, Animal / Q000187:drug effects; D020169:Caspases / Q000235:genetics*; D005625:Frontal Lobe / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006930:Hyperalgesia / Q000188:drug therapy; D007249:Inflammation / Q000201:enzymology / Q000235:genetics; D007279:Injections, Subcutaneous; D053583:Interleukin-1beta / Q000276:immunology; D008297:Male; D051379:Mice; D010126:Ozone / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D010146:Pain / Q000378:metabolism / Q000517:prevention & control*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D010126:Ozone; D020169:Caspases