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Peroxynitrite (ONOO(-)) and species derived from it can oxidize and nitrate lipids, proteins and DNA leading to changes in signaling molecules. The present study was carried out to elucidate possible effects of CNS peroxynitrite in a mouse model of orofacial pain. Mice that received facial carrageenan injection + intracerebroventricular (i.c.v.) injection of the peroxynitrite scavenger [5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinato iron (III), chloride] (FeTPPS) showed significantly fewer face wash strokes upon probing the inflamed area of the face with a von Frey hair at 6 h after injection, compared to mice that received facial carrageenan alone, or facial carrageenan injection + i.c.v. injection of saline. Mice that received i.c.v. injection of FeTPPS without facial carrageenan injection showed no significant difference in response to von Frey hair stimulation, compared to mice that received i.c.v. injection of saline without facial carrageenan injection. These results indicate an anti-nociceptive effect of the peroxynitrite scavenger FeTPPS in carrageenan induced facial pain but no effect on normal tactile sensation and point to an important role of CNS peroxynitrite in nociception.

Increases in several ceramide species have been shown by non-targeted lipid profiling (lipidomics) of the rat hippocampus after kainate lesions (Guan et al. FASEB J 20:1152-1161, 2006). This study was carried out to examine possible effects of ceramide species on exocytosis. Significant increase in membrane capacitance in voltage-clamped rat pheochromocytoma (PC12) cells, an indication of exocytosis, was detected immediately after external application of C2, C6, and C18 ceramide. In contrast, no increase in capacitance was found after addition of C16 and C20 ceramide, or DMSO vehicle. The effect of ceramide on exocytosis was dependent on the integrity of lipid rafts. Treatment of cells with the cholesterol binding agent/disruptor of lipid rafts, methyl beta cyclodextrin, prior to addition of C18 ceramide suppressed the increase in capacitance induced by this lipid species. The ability of C2, C6 and C18 ceramide to trigger exocytosis was confirmed using total internal reflection fluorescence microscopy (TIRFM) experiments. External application of these species caused an exponential decrease in the number of subplasmalemmal neuropeptide Y (NPY)-enhanced green fluorescence protein (EGFP) labeled vesicles, indicating exocytosis. Interestingly, C18 is also the ceramide species that showed the greatest increase in the rat hippocampus after kainate excitotoxicity. It is postulated that C18 ceramide might facilitate exocytosis of glutamate from damaged neurons, thus propagating neuronal injury.

The present study was carried out to determine the effects of central nervous free fatty acids, lysophospholipids, or platelet activating factor (PAF), in a mouse facial carrageenan injection model of orofacial pain. Mice that received intracerebroventricular (I.C.V.) injection of arachidonic acid or oleic acid showed significantly reduced allodynia and behavioral responses to von Frey hair stimulation of a carrageenan-injected area of the face, at 8 h post-injection, compared to controls that received I.C.V. injection of vehicle. In contrast to free fatty acids, increased responses were observed in mice at 72 h after I.C.V. lysophosphatidic acid or lysophosphatidylcholine injection, and at 8 and 24 h after PAF injection, compared vehicle injected controls. Information regarding pro-nociceptive effect of specific brain lipids may be a useful basis for further studies to explore mechanism.