Involvement of neuropeptide Y and Y1 receptor in antinociception in the arcuate nucleus of hypothalamus, an immunohistochemical and pharmacological study in intact rats and rats with inflammation

Neuropeptide Y (NPY) plays an important role in pain modulation at different levels in the central nervous system. In the brain, NPY and NPY receptors distribute abundantly in the arcuate nucleus of hypothalamus (ARC), a structure involved in pain processing. The present study was undertaken to investigate the role of NPY in nociceptive modulation in the ARC of intact rats and rats with carrageenan-induced inflammation. Intra-ARC administration of NPY induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to thermal and mechanical stimulation in intact rats, which was attenuated by the Y1 receptor antagonist NPY28-36. Intra-ARC administration of NPY also induced dose-dependent increases in HWLs to noxious stimulation in rats with inflammation. Furthermore, intra-ARC injection of either the antiserum against NPY or NPY28-36 induced decreases in HWLs in rats with inflammation, while both of them produced no effects in intact ones. Additionally, there were marked increases of Y1 receptor in the bilateral ARC of rats with inflammation tested by immunohistochemistry, while no significant changes of NPY were observed, implicating that the increased Y1 receptor has an important effect in the NPY-induced antinociception. We also found that intra-ARC injection of Y2 receptor agonist NPY3-36 produced no significant antinociception in either intact rats or rats with inflammation. Together, we demonstrate that NPY exerts an antinociceptive effect in the ARC of intact rats and rats with inflammation. Both Y1 receptor and endogenous released NPY in the ARC are involved in the nociceptive modulation during inflammation.