Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia.

Autor:	Boyle KA; Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK., Gradwell MA; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia., Yasaka T; Department of Anatomy and Physiology, Saga University, Saga 849-8501, Japan., Dickie AC; Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK., Polgár E; Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK., Ganley RP; Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK., Orr DPH; Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK., Watanabe M; Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan., Abraira VE; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA., Kuehn ED; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA., Zimmerman AL; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA., Ginty DD; Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA., Callister RJ; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia., Graham BA; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia. Electronic address: brett.graham@newcastle.edu.au., Hughes DI; Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address: david.i.hughes@glasgow.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2019 Jul 09; Vol. 28 (2), pp. 526-540.e6.
DOI:	10.1016/j.celrep.2019.06.040
Abstrakt:	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. (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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