A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord

Technical itch The unpleasant sense of itching, or pruritus, is well known, but its neurobiological basis has remained elusive. Now the first molecular player in the 'itch pathway' has been identified. Historically, itch has been regarded as a less intense variant of the pain sensation. But work with knockout mice shows that the 'gastrin-releasing peptide receptor' is important for communication of itchy, but not painful, stimuli to the central nervous system. This receptor could therefore be a target for the development of antipruritic drugs that do not affect pain signalling. The neurobiological basis of unpleasant sense of itching, or pruritus has been elusive, but this study shows that the 'gastrin releasing peptide receptor' is important for communication of itchy, but not painful, stimuli to the central nervous system. This receptor could therefore be a target for the development of antipruritic drugs that do not affect pain signalling. Itching, or pruritus, is defined as an unpleasant cutaneous sensation that serves as a physiological self-protective mechanism to prevent the body from being hurt by harmful external agents. Chronic itch represents a significant clinical problem resulting from renal diseases and liver diseases, as well as several serious skin diseases such as atopic dermatitis 1 , 2 , 3 . The identity of the itch-specific mediator in the central nervous system, however, remains elusive. Here we describe that the gastrin-releasing peptide receptor (GRPR) plays an important part in mediating itch sensation in the dorsal spinal cord. We found that gastrin-releasing peptide is specifically expressed in a small subset of peptidergic dorsal root ganglion neurons, whereas expression of its receptor GRPR is restricted to lamina I of the dorsal spinal cord. GRPR mutant mice showed comparable thermal, mechanical, inflammatory and neuropathic pain responses relative to wild-type mice. In contrast, induction of scratching behaviour was significantly reduced in GRPR mutant mice in response to pruritogenic stimuli, whereas normal responses were evoked by painful stimuli. Moreover, direct spinal cerebrospinal fluid injection of a GRPR antagonist significantly inhibited scratching behaviour in three independent itch models. These data demonstrate that GRPR is required for mediating the itch sensation rather than pain, at the spinal level. Our results thus indicate that GRPR may represent the first molecule that is dedicated to mediating the itch sens