Defining a Spinal Microcircuit that Gates Myelinated Afferent Input: Implications for Tactile Allodynia.
LTMRs
allodynia
dorsal horn
interneurons
parvalbumin
presynaptic inhibition
touch
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
09 07 2019
09 07 2019
Historique:
received:
10
12
2018
revised:
29
03
2019
accepted:
10
06
2019
entrez:
11
7
2019
pubmed:
11
7
2019
medline:
29
9
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31291586
pii: S2211-1247(19)30806-X
doi: 10.1016/j.celrep.2019.06.040
pmc: PMC6635381
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
526-540.e6Subventions
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/J000620/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P007996/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R35 NS097344
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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