title: Leaky Gate Model: Intensity-Dependent Coding of Pain and Itch in the Spinal Cord.
abstract: Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity, and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin-releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons. When activated, these Grp+neurons generated rarely seen, simultaneous robust pain and itch responses that were intensity dependent. Accordingly, we propose a "leaky gate" model in which Grp+neurons transmit both itch and weak pain signals; however, upon strong painful stimuli, the recruitment of endogenous opioids works to close this gate, reducing overwhelming pain generated by parallel pathways. Consistent with our model, loss of these Grp+neurons increased pain responses while itch was decreased. Our new model serves as an example of non-monotonic coding in the spinal cord and better explains observations in human psychophysical studies.
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Shuohao
authors.initials: S
authors.lastname: Sun
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology and the Center for the Study of Itch, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, 63110, USA.
authors.forename: Changxiong
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology and the Center for the Study of Itch, Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St Louis, MO, 63110, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Solomon H. Snyder Department of Neuroscience and Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: xdong2@jhmi.edu.
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
mesh_terms: D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism / Q000503:physiopathology*; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D009475:Neurons, Afferent / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D011537:Pruritus / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide
keywords: gate control,Grp(+)neuron; itch; leaky gate; neural circuit; pain; spinal cord