First Author | Guo C | Year | 2023 |
Journal | Cell Rep | Volume | 42 |
Issue | 11 | Pages | 113316 |
PubMed ID | 37889748 | Mgi Jnum | J:341998 |
Mgi Id | MGI:7544108 | Doi | 10.1016/j.celrep.2023.113316 |
Citation | Guo C, et al. (2023) Pain and itch coding mechanisms of polymodal sensory neurons. Cell Rep 42(11):113316 |
abstractText | 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. |