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Cell Rep. 2019 Jul 9;28(2):526-540.e6. doi: 10.1016/j.celrep.2019.06.040.

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

Author information

1
Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK.
2
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia.
3
Department of Anatomy and Physiology, Saga University, Saga 849-8501, Japan.
4
Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
5
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
6
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle NSW 2308, Australia. Electronic address: brett.graham@newcastle.edu.au.
7
Spinal Cord Research Group, Institute of Neuroscience and Psychology, University of Glasgow, Glasgow G12 8QQ, UK. Electronic address: david.i.hughes@glasgow.ac.uk.

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.

KEYWORDS:

LTMRs; allodynia; dorsal horn; interneurons; parvalbumin; presynaptic inhibition; touch

PMID:
31291586
DOI:
10.1016/j.celrep.2019.06.040
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