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

被引:576
作者
Sun, Yan-Gang
Chen, Zhou-Feng [1 ]
机构
[1] Washington Univ, Sch Med, Pain Ctr, Dept Anesthesiol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Pain Ctr, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Pain Ctr, Dept Psychiat, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1038/nature06029
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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(1-3). 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 sensation in the dorsal horn of the spinal cord, and thus may provide a central therapeutic target for antipruritic drug development.
引用
收藏
页码:700 / U10
页数:5
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