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

作者：Kieran A. Boyle, Erika Polgár, María Gutièrrez‐Mecinas, Allen C. Dickie, Andrew H. Cooper, Andrew M. Bell, Evelline Jumolea, Adrián Casas-Benito, Masahiko Watanabe, David I. Hughes, Greg A. Weir, John S. Riddell, Andrew J. Todd · 发表于：eLife · 年份：2023 · DOI：10.7554/elife.86633 · 被引用次数：38 · 研究领域：Pain Mechanisms and Treatments、Dermatology and Skin Diseases、Neuropeptides and Animal Physiology

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.