Abstract
Neuropeptide Y (NPY) is a highly conserved neuropeptide with widespread distribution in the central nervous system and diverse physiological functions. While extensively studied for its inhibitory effects on pain at the spinal cord level, its role in pain modulation within the brain remains less clear. This review aims to summarize the complex landscape of supraspinal NPY signaling in pain processing. We discuss the expression and function of NPY receptors in key pain-related brain regions, including the parabrachial nucleus, periaqueductal gray, amygdala, and nucleus accumbens. Additionally, we highlight the potent efficacy of NPY in attenuating pain sensitivity and nociceptive processing throughout the central nervous system. NPY-based therapeutic interventions targeting the central nervous system represent a promising avenue for novel analgesic strategies and pain-associated comorbidities.