Spinal GRP mediates itch in nonhuman primates

Abstract

More than 30 years ago, it was found that bombesin originally isolated form frog skin caused scratching ⁄ grooming behaviors in mammals. Subsequently, gastrin–releasing peptide (GRP) and neuromedin B (NMB) were identified as endogenous bombesin family peptides, and those peptides elicited scratching behaviors following intrathecal administration in rodents. After the characterization of GRP receptor (GRPR)–expressing neurons in the spinal dorsal horn in 2007, the understanding of itch transmission has markedly advanced in this 10 years. In both rodents and non­human primates, exogenously administered GRP elicits robust scratching behaviors, indicating that activation of GRPR+ neurons is responsible for itch. However, based on several lines of evidence, regulatory mechanisms of GRPR+ neurons are very complicated. A majority of peripherally elicited itch are abolished by ablation of GRPR+ neurons, whereas GRPR antagonist or GRPR–deficiency has limited effects on peri­pherally elicited itch. These facts suggest that GRPR+ neurons are activated by not only GRP but also other transmitters such as glutamate. Although there are limited studies for pathological mechanisms of itch, some reports suggest that enhancement of GRP–GRPR system underlies spinal regulation of chronic itch. Given the functional similarities of GRP between rodents and nonhuman primates, it is important to study the detailed mechanisms of GRP–GRPR systems mediating physiological and pathological itch.