TAFA4 Reverses Mechanical Allodynia through Activation of GABAergic Transmission and Microglial Process Retraction
Cell Reports. 2018-03-01; 22(11): 2886-2897
DOI: 10.1016/j.celrep.2018.02.068
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1. Cell Rep. 2018 Mar 13;22(11):2886-2897. doi: 10.1016/j.celrep.2018.02.068.
TAFA4 Reverses Mechanical Allodynia through Activation of GABAergic Transmission
and Microglial Process Retraction.
Kambrun C(1), Roca-Lapirot O(1), Salio C(2), Landry M(1), Moqrich A(3), Le Feuvre
Y(4).
Author information:
(1)Interdisciplinary Institute for Neuroscience, University Bordeaux, UMR 5297,
33000 Bordeaux, France; Interdisciplinary Institute for Neuroscience, CNRS, UMR
5297, 33000 Bordeaux, France.
(2)Department of Veterinary Sciences, University of Turin, 10095 Grugliasco (TO),
Italy.
(3)Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de
Marseille, UMR 7288, Case 907, 13288 Cedex 09, France.
(4)Interdisciplinary Institute for Neuroscience, University Bordeaux, UMR 5297,
33000 Bordeaux, France; Interdisciplinary Institute for Neuroscience, CNRS, UMR
5297, 33000 Bordeaux, France. Electronic address: .
C-low-threshold mechanoreceptors (C-LTMRs) are sensory neurons that, beyond
conveying pleasant touch, modulate nociceptive transmission within the spinal
cord. However, pain alleviation by C-LTMRs remains poorly understood. Here, we
show that the C-LTMR-derived TAFA4 chemokine induces a reinforcement of
inhibitory synaptic transmission within spinal networks, which consequently
depresses local excitatory synapses and impairs synaptic transmission from
high-threshold C-fibers. In animals with inflammation induced by Freund’s
complete adjuvant, TAFA4 decreases the noxious stimulus-induced neuronal
responses recorded in vivo and alleviates mechanical pain. Both effects are
blocked by antagonists of GABAergic transmission. Furthermore, TAFA4 promotes
microglial retraction in inflammation and increases the number of inhibitory
synapses on lamina IIi somata. Altogether, these results demonstrate GABAergic
interneurons to be the first integration relay for C-LTMRs and highlight a tight
interplay between sensory neurons, microglial cells, and spinal interneurons,
which fine-tunes inhibitory activity and nociceptive transmission in pathological
conditions.
Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
DOI: 10.1016/j.celrep.2018.02.068
PMID: 29539418 [Indexed for MEDLINE]