Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord

Kardon, A. P. et al. (2014) Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord. Neuron, 82(3), pp. 573-586. (doi: 10.1016/j.neuron.2014.02.046) (PMID:24726382) (PMCID:PMC4022838)

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Abstract

Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5−/− mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hachisuka, Dr Junichi and Beresford-Polgar, Dr Erika and Todd, Professor Andrew
Authors: Kardon, A. P., Polgár, E., Hachisuka, J., Snyder, L. M., Cameron, D., Savage, S., Cai, X., Karnup, S., Fan, C. R., Hemenway, G. M., Bernard, C. S., Schwartz, E. S., Nagase, H., Schwarzer, C., Watanabe, M., Furuta, T., Kaneko, T., Koerber, H. R., Todd, A. J., and Ross, S. E.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Neuron
Publisher:Elsevier (Cell Press)
ISSN:0896-6273
ISSN (Online):1097-4199
Published Online:10 April 2014
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Neuron 82(3):573-586
Publisher Policy:Reproduced under a Creative Commons License

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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