Supraspinally Applied Nitric Oxide Donors Exert a Dual Action on Thermal Nociception in Mice

Abstract

To clarify the complex role of brain nitric oxide (NO) in nociceptive processing, we examined the effects of intracerebroventricular NO donors on thermal nociception and on the thermal antinociception induced by intracerebroventricular NO synthase inhibitors, as assessed by the tail-flick test in mice. Sodium nitroprusside, an NO donor, when administered intracerebroventricularly, slightly but significantly prolonged the tail-flick latency at relatively low doses, 0·1–1 μg per mouse, whereas it produced no effect at 10 μg per mouse. Similarly, intracerebroventricular S-nitroso-N-acetylpenicillamine (SNAP), another NO donor, exerted a small antinociceptive effect at 0·1 μg per mouse, while it was without effect at 1–10 μg per mouse. Sodium nitroprusside or SNAP administered intracerebroventricularly at 10 μg per mouse, a dose which failed to elicit an effect by itself, drastically reversed the antinociception induced by intracerebroventricular administration of N-iminoethyl-L-ornithine or NG-nitro-L-arginine methyl ester, both NO synthase inhibitors, at 3 μg per mouse. Thus, supraspinally applied NO donors exert a dual action on thermal nociception in mice, thereby suggesting that brain NO is pro-nociceptive, but may also have an antinociceptive property.