Pain Inhibits GRPR Neurons via GABAergic Signaling in the Spinal Cord

It has been known that algogens and cooling could inhibit itch sensation; however, the underlying molecular and neural mechanisms remain poorly understood. Here, we show that the spinal neurons expressing gastrin releasing peptide receptor (GRPR) primarily comprise excitatory interneurons that recei...

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Bibliographic Details
Published in:Scientific reports 2019-11, Vol.9 (1), p.15804-11, Article 15804
Main Authors: Bardoni, Rita, Shen, Kai-Feng, Li, Hui, Jeffry, Joseph, Barry, Devin M., Comitato, Antonella, Li, Yun-Qing, Chen, Zhou-Feng
Format: Article
Language:English
Subjects:
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631/378/3919
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Animals
Capsaicin
Fibers
Gastrin
Humanities and Social Sciences
Interneurons
multidisciplinary
Neurokinin
Neurokinin NK1 receptors
Neurons - metabolism
Pain
Pain - metabolism
Pain - pathology
Receptors, Bombesin - metabolism
Science
Science (multidisciplinary)
Signal Transduction
Spinal cord
Synaptic transmission
γ-Aminobutyric acid
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Summary:It has been known that algogens and cooling could inhibit itch sensation; however, the underlying molecular and neural mechanisms remain poorly understood. Here, we show that the spinal neurons expressing gastrin releasing peptide receptor (GRPR) primarily comprise excitatory interneurons that receive direct and indirect inputs from C and Aδ fibers and form contacts with projection neurons expressing the neurokinin 1 receptor (NK1R). Importantly, we show that noxious or cooling agents inhibit the activity of GRPR neurons via GABAergic signaling. By contrast, capsaicin, which evokes a mix of itch and pain sensations, enhances both excitatory and inhibitory spontaneous synaptic transmission onto GRPR neurons. These data strengthen the role of GRPR neurons as a key circuit for itch transmission and illustrate a spinal mechanism whereby pain inhibits itch by suppressing the function of GRPR neurons.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-52316-0