Progress in the study of itch gating mechanism

On December 5, the Journal of the National Academy of Sciences published a research paper on the regulation of GRPR positive neurons in the spinal cord by local and long-range inhibitory projections The research was completed by sun Yangang research group, brain science and Intelligent Technology Innovation Center (Institute of Neuroscience), National Key Laboratory of neuroscience, Chinese Academy of Sciences Pruritus is a kind of body sensation different from pain, warmth and touch, which can induce conservative scratching behavior in many kinds of animals, such as human beings However, for patients with chronic pruritus, persistent scratching caused by pruritus can lead to skin damage, infection and abnormal pain In order to alleviate the pain caused by chronic itch, we need to understand the neural mechanism of itch signal processing and regulation Neurons expressing gastrin releasing peptide receptor +, GRPR +, in the dorsal horn of the spinal cord play an important role in the process of itching signal processing However, how these neurons are regulated by the local and long-term inhibitory circuits of the spinal cord is unknown The team combined photogenetics and patch clamp electrophysiological recording to find that galanin + neurons, a subgroup of inhibitory interneurons in the dorsal horn of the spinal cord, form inhibitory synaptic connections with GRPR + neurons in the dorsal horn of the spinal cord, and play a key role in the gating of GRPR + neuron dependent itch signal transmission Activation of galanin + neurons in the dorsal horn of the spinal cord can inhibit the scratching behavior induced by various itching agents, but not affect the pain perception behavior of mice; killing these neurons can enhance the scratching behavior induced by itching agents In addition, GRPR + neurons in the spinal cord also receive inhibitory input and 5-hydroxytryptamine input from rostral ventromedial medulla (RVM) Therefore, both local inhibition loop and long-term inhibition projection can directly regulate GRPR + neuron activity and then gate the processing of itch signals at spinal cord level In this study, the mechanism of itch signal pathway gated by local spinal cord loop and long-term medulla oblongata loop was analyzed Under the guidance of researcher sun Yangang, doctoral students Liu Mingzhe and Chen Xiaojun are the co first authors of this paper At the same time, Liang Tongyu, Wang Meng, Zhang Xinyan and Li Qing of the research group also made important contributions, and they were greatly assisted by researcher sun Qiang and assistant researcher Li Yuzhuo Confocal imaging, fluorescence microscopy and other related work were completed in the optical imaging platform of brain intelligence center of excellence Hu Qian, Xiang Dan, Chen Xuxin, Wang Yonghong and Zhang Yumei provided help in data collection and analysis This work was supported by the National Natural Science Foundation of China and major special projects of Shanghai.