Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

Boyle, K. A. et al. (2023) Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling. eLife, (doi: 10.7554/eLife.86633.1) (Early Online Publication)

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Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here we investigate the role of interneurons that continue to express NPY (NPY-INs) in adulthood. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen- evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY- IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.

Item Type:Articles
Status:Early Online Publication
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Hughes, Dr David I and Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew and Riddell, Professor John and Cooper, Dr Andrew and Weir, Dr Gregory and Dickie, Dr Allen and Gutierrez-Mecinas, Dr Maria and Casas Benito, Adrian
Authors: Boyle, K. A., Polgár, E., Gutierrez-Mecinas, M., Dickie, A. C., Cooper, A. H., Bell, A. M., Jumolea, M. E., Casas-Benito, A., Watanabe, M., Hughes, D. I., Weir, G. A., Riddell, J. S., and Todd, A. J.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:eLife
Publisher:eLife Sciences Publications
ISSN (Online):2050-084X
Published Online:29 March 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in eLife 2023
Publisher Policy:Reproduced under a Creative Commons licence

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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
172232The role of NPY-containing inhibitory interneurons in spinal pain pathwaysAndrew ToddBiotechnology and Biological Sciences Research Council (BBSRC)BB/N006119/1Centre for Neuroscience
174050Determining the role of calretinin-RorB spinal interneurons in modulating mechanical painDavid I HughesBiotechnology and Biological Sciences Research Council (BBSRC)BB/P007996/1School of Psychology and Neuroscience
302893Neuronal circuits for itch in the spinal dorsal hornAndrew ToddMedical Research Council (MRC)MR/S002987/1Centre for Neuroscience
307631Dissecting the relative contributions of injured and intact primary afferents to neuronal plasticity and neuropathic painGregory WeirMedical Research Council (MRC)MR/T01072X/1Centre for Neuroscience
312478The roles of functionally defined populations of lamina I projection neuronsJunichi HachisukaMedical Research Council (MRC)MR/V033638/1Centre for Neuroscience