Opposing interplay between Neuropeptide FF and nitric oxide in antinociception and hypothermia

This study examined the ability of the anti-opioid Neuropeptide FF (NPFF) t o modify the endogenous activity of nitric oxide (NO). Antinociceptive and hypothermic effects of 1DMe (D.Tyr-Leu-(N.Me)Phe-Gln-Pro-Gln-Arg-Phe-NH2), an NPFF agonist, and of L-NAME (N(omega)nitro-L-arginine methyl eater), an inhibitor of nitric oxide synthase, were investigated in mice. Intraperiton eal (i.p.) injection of L-NAME induced, in the hot plate test, a dose-depen dent antinociception not reversed by naloxone, an opioid antagonist, but in hibited by L-Arg, the NO synthesis precursor. Intracerebroventricular (i.c. v.) injections of 1DMe inhibit the antinociceptive activity of L-NAME in a dose-dependent manner. On the contrary, L-NAME markedly potentiated hypothe rmia induced by 1DMe injected in the third ventricle. These data show that Neuropeptide FF receptors exert a dual effect on endogenous NO functions an d could modulate pain transmission independently of opioids. (C) 2000 Elsev ier Science Inc. All rights reserved.