4.8 Article

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

Journal

ELIFE
Volume 12, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.86633

Keywords

NPY; chemogenetics; neuropathic pain; inflammatory pain; pruritogen

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This study investigates the role of interneurons that continue to express neuropeptide Y (NPY-INs) in the adult mouse spinal cord. The findings suggest that activation of NPY-INs reduces acute pain and pruritogen-evoked itch, while silencing them causes exaggerated itch responses. Silencing another population of inhibitory interneurons also increases itch, but to a lesser extent.
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.

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