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

Author:

Boyle Kieran A1ORCID,Polgar Erika1,Gutierrez-Mecinas Maria1,Dickie Allen C1ORCID,Cooper Andrew H1ORCID,Bell Andrew M1ORCID,Jumolea Evelline1,Casas-Benito Adrian1ORCID,Watanabe Masahiko2ORCID,Hughes David I1ORCID,Weir Gregory A1,Riddell John S1,Todd Andrew J1ORCID

Affiliation:

1. School of Psychology and Neuroscience, College of Medical, Veterinary and Life Sciences, University of Glasgow

2. Department of Anatomy, Hokkaido University School of Medicine

Abstract

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 the adult mouse spinal cord. 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.

Funder

Wellcome Trust

Biotechnology and Biological Sciences Research Council

Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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