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

Kieran A Boyle; Mark A Gradwell; Toshiharu Yasaka; Allen C Dickie; Erika Polgár; Robert P Ganley; Desmond P H Orr; Masahiko Watanabe; Victoria E Abraira; Emily D Kuehn; Amanda L Zimmerman; David D Ginty; Robert J Callister; Brett A Graham; David I Hughes

doi:10.1016/j.celrep.2019.06.040

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

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

Kieran A Boyle, Mark A Gradwell, Toshiharu Yasaka, Allen C Dickie, Erika Polgár, Robert P Ganley, Desmond P H Orr, Masahiko Watanabe, Victoria E Abraira, Emily D Kuehn, …

Cell reports (Cambridge), Vol.28(2), pp.526-540.e6

07/09/2019

DOI: https://doi.org/10.1016/j.celrep.2019.06.040

PMCID: PMC6635381

PMID: 31291586

Abstract

Mice

Animals

Hyperalgesia - genetics

Myelin Sheath - pathology

Mechanoreceptors

Chronic Pain

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.

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Title: Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia
Creators: Kieran A Boyle - Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK
Mark A Gradwell - School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia
Toshiharu Yasaka - Department of Anatomy and Physiology, Saga University, Saga 849-8501, Japan
Allen C Dickie - Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK
Erika Polgár - Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK
Robert P Ganley - Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK
Desmond P H Orr - Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK
Masahiko Watanabe - Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan
Victoria E Abraira - Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Emily D Kuehn - Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Amanda L Zimmerman - Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
David D Ginty - Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA
Robert J Callister - School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia
Brett A Graham - School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia. Electronic address: brett.graham@newcastle.edu.au
David I Hughes - Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address: david.i.hughes@glasgow.ac.uk
Publication Details: Cell reports (Cambridge), Vol.28(2), pp.526-540.e6
Date published: 07/09/2019
Grant note: BB/P007996/1 / Biotechnology and Biological Sciences Research Council Howard Hughes Medical Institute BB/J000620/1 / Biotechnology and Biological Sciences Research Council R35 NS097344 / NINDS NIH HHS
Academic Unit: Cell Biology and Neuroscience (SAS); W.M. Keck Center of Collaborative Neuroscience
Language: English
Resource Type: Journal article
Identifiers: 991031654809704646