Circuit dissection of the role of somatostatin in itch and pain

Huang, J. et al. (2018) Circuit dissection of the role of somatostatin in itch and pain. Nature Neuroscience, 21(5), pp. 707-716. (doi:10.1038/s41593-018-0119-z) (PMID:29556030) (PMCID:PMC5923877)

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Abstract

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Riddell, Dr John and Dickie, Dr Allen and Beresford-Polgar, Dr Erika and Todd, Professor Andrew
Authors: Huang, J., Polgár, E., Solinski, H. J., Mishra, S. K., Tseng, P.-Y., Iwagaki, N., Boyle, K. A., Dickie, A. C., Kriegbaum, M. C., Wildner, H., Zeilhofer, H. U., Watanabe, M., Riddell, J. S., Todd, A. J., and Hoon, M. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Nature Neuroscience
Publisher:Nature Publishing Group
ISSN:1097-6256
ISSN (Online):1546-1726
Published Online:19 March 2018
Copyright Holders:Copyright © 2018 Nature America Inc., part of Springer Nature
First Published:First published in Nature Neuroscience 21(5):707-716
Publisher Policy:Reproduced in accordance with the publisher copyright policy
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
627371Spinal inhibitory interneurons that suppress itchAndrew ToddMedical Research Council (MRC)MR/L003430/1INP - CENTRE FOR NEUROSCIENCE
689031The role of NPY-containing inhibitory interneurons in spinal pain pathwaysAndrew ToddBiotechnology and Biological Sciences Research Council (BBSRC)BB/N006119/1INP - CENTRE FOR NEUROSCIENCE
644161Defining pain circuitry in health and diseaseAndrew ToddWellcome Trust (WELLCOTR)102645/Z/13/ZINP - CENTRE FOR NEUROSCIENCE