Role of Central Nervous Peroxynitrite in Orofacial Pain

Objective: Nitric oxide may combine with superoxide to form peroxynitrite (ONOO-). The latter is a non-radical produced by a very fast reaction of NO and the superoxide (O2.-) radical. It is a highly toxic and reactive intermediate, which has been strongly implicated in a number of NO cytotoxicity models. The present study was carried out to elucidate the effect of central nervous nitric oxide and peroxynitrite in a mouse model of nociception from the orofacial region. Methods: C57BL/6J mice received a facial injection of the chronic inflammatory agent, carrageenan, and an intracerebroventricular (i.c.v.) injection of the nitric oxide donor (DETA NONOate, or NOC-18), nitric oxide scavenger (carboxy-PTIO), peroxynitrite donor (SIN-1) or peroxynitrite decomposition catalyst (iron tetrakis), or saline (controls). The number of behavioral responses to mechanical stimulation using a von Frey hair i.e. detection, withdrawal, escape / attack, scratching, was quantified after injection. The mean and standard deviations of the total responses were calculated for each group of treated mice, and possible significant differences between their means elucidated (1-way ANOVA with Bonferroni's multiple comparison post hoc test). Results: Significantly reduced responses were observed after injection of the nitric oxide donor (2 and 15 µg), whereas no difference was observed after injection of the nitric oxide scavenger (3 and 15 µg). In comparison, no difference was observed after injection of the peroxynitrite donor (2 and 50 µg), but significantly reduced responses was detected after injection with the peroxynitrite decomposition catalyst (1.5, 3.0, and 7.5 µg). Conclusion: The above results show that endogenous central nervous peroxynitrite play a role in enhancing nociceptive transmission from the orofacial region. Further studies are necessary to elucidate the role of central nervous peroxynitrite in pain from other parts of the body.