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

Boyle, K. A.; Polgar, E.; Gutierrez-Mecinas, M.; Dickie, A. C.; Cooper, A. H.; Bell, A. M.; Jumolea, E.; Casas-Benito, A.; Watanabe, M.; Hughes, D. I.; Weir, G.; Riddell, J.; Todd, A. J.

doi:10.1101/2023.02.10.528013

bioRxiv · 10.1101/2023.02.10.528013

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

Boyle, K. A.·Polgar, E.·Gutierrez-Mecinas, M.·Dickie, A. C.·Cooper, A. H.·Bell, A. M.·Jumolea, E.·Casas-Benito, A.·Watanabe, M.·Hughes, D. I.·Weir, G.·Riddell, J.·Todd, A. J.

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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 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.

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Boyle, K. A., Polgar, E., Gutierrez-Mecinas, M., Dickie, A. C., Cooper, A. H., Bell, A. M., Jumolea, E., Casas-Benito, A., Watanabe, M., Hughes, D. I., Weir, G., Riddell, J., Todd, A. J.. 2023-02-10. Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling. https://doi.org/10.1101/2023.02.10.528013

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