Defining a spinal microcircuit that gates myelinated afferent input: implications for tactile allodynia

Boyle, K. A. et al. (2019) Defining a spinal microcircuit that gates myelinated afferent input: implications for tactile allodynia. Cell Reports, 28(2), 526-540.e6. (doi: 10.1016/j.celrep.2019.06.040) (PMID:31291586) (PMCID:PMC6635381)

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Abstract

Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate the passage of sensory information conveyed by low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate the polysynaptic relay of LTMR input to pain circuits by inhibiting lamina II excitatory interneurons whose axons project into lamina I. We show changes in the functional properties of these PV interneurons following peripheral nerve injury and that silencing these cells unmasks a circuit that allows innocuous touch inputs to activate pain circuits by increasing network activity in laminae I–IV. Such changes are likely to result in the development of tactile allodynia and could be targeted for more effective treatment of mechanical pain.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Hughes, Dr David I and Dickie, Dr Allen and Beresford-Polgar, Dr Erika and Yasaka, Dr Toshiharu
Authors: Boyle, K. A., Gradwell, M. A., Yasaka, T., Dickie, A. C., Polgár, E., Ganley, R. P., Orr, D. P.H., Watanabe, M., Abraira, V. E., Kuehn, E. D., Zimmerman, A. L., Ginty, D. D., Callister, R. J., Graham, B. A., and Hughes, D. I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Cell Reports
Publisher:Elsevier (Cell Press)
ISSN:2211-1247
ISSN (Online):2211-1247
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Cell Reports 28(2): 526-540.e6
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
571071Modulating cutaneous afferent input: Identifying a source of presynaptic (axo-axonic) inputs in the mouse spinal dorsal hornDavid I HughesBiotechnology and Biological Sciences Research Council (BBSRC)BB/J000620/1RI NEUROSCIENCE & PSYCHOLOGY
737031Determining the role of calretinin-RorB spinal interneurons in modulating mechanical painDavid I HughesBiotechnology and Biological Sciences Research Council (BBSRC)BB/P007996/1INP - CENTRE FOR NEUROSCIENCE