Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain

Polgár, E. et al. (2022) Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain. Pain, (doi: 10.1097/j.pain.0000000000002677) (PMID:35543635) (Early Online Publication)

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Abstract

Neurons in the superficial dorsal horn that express the gastrin-releasing peptide receptor (GRPR) are strongly implicated in spinal itch pathways. However, a recent study reported that many of these correspond to vertical cells, a population of interneurons that are thought to transmit nociceptive information. In this study, we have used a GRPRCreERT2 mouse line to identify and target cells that possess Grpr mRNA. We find that the GRPR cells are highly concentrated in lamina I and the outer part of lamina II, that they are all glutamatergic, and that they account for ∼15% of the excitatory neurons in the superficial dorsal horn. We had previously identified 6 neurochemically distinct excitatory interneuron populations in this region based on neuropeptide expression and the GRPR cells are largely separate from these, although they show some overlap with cells that express substance P. Anatomical analysis revealed that the GRPR neurons are indeed vertical cells, and that their axons target each other, as well as arborising in regions that contain projection neurons: lamina I, the lateral spinal nucleus and the lateral part of lamina V. Surprisingly, given the proposed role of GRPR cells in itch, we found that most of the cells received monosynaptic input from Trpv1-expressing (nociceptive) afferents, that the great majority responded to noxious and pruritic stimuli, and that chemogenetically activating them resulted in pain- and itch-related behaviours. Together, these findings suggest that the GRPR cells are involved in spinal cord circuits that underlie both pain and itch.

Item Type:Articles
Status:Early Online Publication
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew and Quillet, Dr Raphaelle and Riddell, Professor John and Dickie, Dr Allen and Gutierrez-Mecinas, Dr Maria
Authors: Polgár, E., Dickie, A. C., Gutierrez-Mecinas, M., Bell, A. M., Boyle, K. A., Quillet, R., Rashid, E. A., Clark, R. A., German, M. T., Watanabe, M., Riddell, J. S., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Pain
Publisher:Lippincott, Williams & Wilkins
ISSN:0304-3959
ISSN (Online):1872-6623
Published Online:11 May 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Pain 2022
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
308174Spinal circuits underlying pathological painAndrew ToddWellcome Trust (WELLCOTR)219433/Z/19/ZCentre for Neuroscience
302893Neuronal circuits for itch in the spinal dorsal hornAndrew ToddMedical Research Council (MRC)MR/S002987/1Centre for Neuroscience
312478The roles of functionally defined populations of lamina I projection neuronsJunichi HachisukaMedical Research Council (MRC)MR/V033638/1Centre for Neuroscience