Pain and itch coding mechanisms of polymodal sensory neurons
Changxiong Guo,
Haowu Jiang,
Cheng-Chiu Huang,
Fengxian Li,
William Olson,
Weishan Yang,
Michael Fleming,
Guang Yu,
George Hoekel,
Wenqin Luo,
Qin Liu
Affiliations
Changxiong Guo
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
Haowu Jiang
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
Cheng-Chiu Huang
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
Fengxian Li
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
William Olson
Department of Neuroscience, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
Weishan Yang
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
Michael Fleming
Department of Neuroscience, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
Guang Yu
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
George Hoekel
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA
Wenqin Luo
Department of Neuroscience, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104, USA
Qin Liu
Washington University Pain Center, Department of Anesthesiology, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA; Corresponding author
Summary: 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.
