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Dorsal Horn Gastrin-Releasing Peptide Expressing Neurons Transmit Spinal Itch But Not Pain Signals

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Albisetti Gioele W., Pagani Martina, Platonova Evgenia, Hösli Ladina, Johannssen Helge C., Fritschy Jean-Marc, Wildner Hendrik, Zeilhofer Hanns Ulrich,
Project Dorsal Horn Neuronal Circuits Processing Itch
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Original article (peer-reviewed)

Journal The Journal of Neuroscience
Volume (Issue) 39(12)
Page(s) 2238 - 2250
Title of proceedings The Journal of Neuroscience
DOI 10.1523/jneurosci.2559-18.2019

Open Access

Type of Open Access Publisher (Gold Open Access)


Gastrin-releasing peptide (GRP) is a spinal itch transmitter expressed by a small population of dorsal horn interneurons (GRP neurons). The contribution of these neurons to spinal itch relay is still only incompletely understood, and their potential contribution to pain-related behaviors remains controversial. Here, we have addressed this question in a series of experiments performed in GRP::cre and GRP::eGFP transgenic male mice. We combined behavioral tests with neuronal circuit tracing, morphology, chemogenetics, optogenetics, and electrophysiology to obtain a more comprehensive picture. We found that GRP neurons form a rather homogeneous population of central cell-like excitatory neurons located in lamina II of the superficial dorsal horn. Multicolor high-resolution confocal microscopy and optogenetic experiments demonstrated that GRP neurons receive direct input from MrgprA3-positive pruritoceptors. Anterograde HSV-based neuronal tracing initiated from GRP neurons revealed ascending polysynaptic projections to distinct areas and nuclei in the brainstem, midbrain, thalamus, and the somatosensory cortex. Spinally restricted ablation of GRP neurons reduced itch-related behaviors to different pruritogens, whereas their chemogenetic excitation elicited itch-like behaviors and facilitated responses to several pruritogens. By contrast, responses to painful stimuli remained unaltered. These data confirm a critical role of dorsal horn GRP neurons in spinal itch transmission but do not support a role in pain.