Bourane Steeve, Duan Bo, Koch Stephanie C, Dalet Antoine, Britz Olivier, Garcia-Campmany Lidia, Kim Euiseok, Cheng Longzhen, Ghosh Anirvan, Ma Qiufu, Goulding Martyn
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA.
Science. 2015 Oct 30;350(6260):550-4. doi: 10.1126/science.aac8653.
Light mechanical stimulation of hairy skin can induce a form of itch known as mechanical itch. This itch sensation is normally suppressed by inputs from mechanoreceptors; however, in many forms of chronic itch, including alloknesis, this gating mechanism is lost. Here we demonstrate that a population of spinal inhibitory interneurons that are defined by the expression of neuropeptide Y::Cre (NPY::Cre) act to gate mechanical itch. Mice in which dorsal NPY::Cre-derived neurons are selectively ablated or silenced develop mechanical itch without an increase in sensitivity to chemical itch or pain. This chronic itch state is histamine-independent and is transmitted independently of neurons that express the gastrin-releasing peptide receptor. Thus, our studies reveal a dedicated spinal cord inhibitory pathway that gates the transmission of mechanical itch.
对有毛皮肤进行轻度机械刺激可诱发一种称为机械性瘙痒的瘙痒形式。这种瘙痒感觉通常会被机械感受器的输入所抑制；然而，在许多形式的慢性瘙痒中，包括感觉异常性疼痛，这种门控机制会丧失。在这里，我们证明了一群由神经肽Y::Cre（NPY::Cre）表达所定义的脊髓抑制性中间神经元起到了门控机械性瘙痒的作用。在背侧NPY::Cre衍生神经元被选择性切除或沉默的小鼠中，会出现机械性瘙痒，而对化学性瘙痒或疼痛的敏感性并未增加。这种慢性瘙痒状态与组胺无关，并且独立于表达胃泌素释放肽受体的神经元进行传递。因此，我们的研究揭示了一条专门的脊髓抑制通路，该通路可门控机械性瘙痒的传递。
