Pain and itch coding mechanisms of polymodal sensory neurons

作者：Changxiong Guo, Haowu Jiang, Cheng-Chiu Huang, Fengxian Li, William Olson, Weishan Yang, Michael S. Fleming, Guang Yu, George E. Hoekel, Wenqin Luo, Qin Liu · 发表于：Cell Reports · 年份：2023 · DOI：10.1016/j.celrep.2023.113316 · 被引用次数：31 · 研究领域：Pain Mechanisms and Treatments、Neurobiology and Insect Physiology Research、Dermatology and Skin Diseases

Pain and itch coding mechanisms in polymodal sensory neurons remain elusive. MrgprD + neurons represent a major polymodal population and mediate both mechanical pain and nonhistaminergic itch. Here, we show that chemogenetic activation of MrgprD + neurons elicited both pain- and itch-related behavior in a dose-dependent manner, revealing an unanticipated compatibility between pain and itch in polymodal neurons. While VGlut2-dependent glutamate release is required for both pain and itch transmission from MrgprD + neurons, the neuropeptide neuromedin B (NMB) is selectively required for itch signaling. Electrophysiological recordings further demonstrated that glutamate synergizes with NMB to excite NMB-sensitive postsynaptic neurons. Ablation of these spinal neurons selectively abolished itch signals from MrgprD + neurons, without affecting pain signals, suggesting a dedicated itch-processing central circuit. These findings reveal distinct neurotransmitters and neural circuit requirements for pain and itch signaling from MrgprD + polymodal sensory neurons, providing new insights on coding and processing of pain and itch.