Antinociceptive effects of neuropeptide Y and related peptides in mice

This study compares the antinociceptive and orexigenic activities of NPY and analogs after intracerebroventricular administration in mice. NPY had an antinociceptive action in the mouse writhing test which was not affected by Drier treatment with naltrexone. yohimbine, idazoxan or reserpine. A detailed examination revealed that NPY (0.023-0.7 nmol), PYY (0.007-0.07 nmol), NPY2-36 (0.023-0.23 nmol) and the Y-1 agonist [Leu(31),Pro(34)]-NPY (0.07-0.7 nmol) all produced a dose-dependent and complete suppression of acetic acid-induced writhing. In contrast, the Y-2 agonist, NPY13-26, had little or no antinociceptive effect. As shown by their ED(50) values, the relative potency of the peptides was PYY > NPY2-36 greater than or equal to NPY > [Leu(31),Pro(34)]-NPY much greater than NPY13-36, suggesting that a Y-1 rather than a Y-2 or Y-3 receptor subtype was implicated in the antinociceptive action. Thereafter, all peptides were assessed for their effects on food intake. With respect to dose and peptide specificity, the hyperphagic effects of NPY and related peptides paralleled those on nociception, suggesting a common receptor mechanism. However, a purported NPY antagonist, [D-Trp(32)]-NPY, attenuated NPY's effect on feeding yet this same peptide elicited a dose-dependent inhibition of acetic acid-induced writhing, suggesting some molecular distinction between antinociception and stimulation of food intake.