Neuropeptide Y and its Involvement in Chronic Pain

•NPY is a neuropeptide widely expressed in the peripheral and central nervous systems.•NPY expression is increased in the dorsal horn of animal models of chronic pain.•NPY Y1 and Y2 receptors are implicated in pain modulation in the spinal cord.•Intrathecal administration of NPY produces analgesia in animal models of chronic pain. Chronic pain is a serious condition that significantly impairs the quality of life, affecting an estimate of 1.5 billion people worldwide. Despite the physiological, emotional and financial burden of chronic pain, there is still a lack of efficient treatments. Neuropeptide Y (NPY) is a highly conserved endogenous peptide in the central and peripheral nervous systems of all mammals, which has been implicated in both pro- and antinociceptive effects. NPY is expressed in the superficial laminae of the dorsal horn of the spinal cord, where it appears to mediate its antinociceptive actions via the Y1 and Y2 receptors. Intrathecal administration of NPY in animal models of neuropathic, inflammatory or postoperative pain has been shown to cause analgesia, even though its exact mechanisms are still unclear. It remains to be seen whether these promising central antinociceptive effects of NPY can be transferred into a future treatment for chronic pain.