TY - JOUR
T1 - Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain
AU - van der Vlist, Michiel
AU - Raoof, Ramin
AU - Willemen, Hanneke L D M
AU - Prado, Judith
AU - Versteeg, Sabine
AU - Martin Gil, Christian
AU - Vos, Martijn
AU - Lokhorst, Roeland E
AU - Pasterkamp, R Jeroen
AU - Kojima, Toshiyuki
AU - Karasuyama, Hajime
AU - Khoury-Hanold, William
AU - Meyaard, Linde
AU - Eijkelkamp, Niels
N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2022/2/16
Y1 - 2022/2/16
N2 - The current paradigm is that inflammatory pain passively resolves following the cessation of inflammation. Yet, in a substantial proportion of patients with inflammatory diseases, resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight into how inflammatory pain is resolved is lacking. Here, we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. The resolution of pain and the transfer of mitochondria requires expression of CD200 receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain.
AB - The current paradigm is that inflammatory pain passively resolves following the cessation of inflammation. Yet, in a substantial proportion of patients with inflammatory diseases, resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain. Mechanistic insight into how inflammatory pain is resolved is lacking. Here, we show that macrophages actively control resolution of inflammatory pain remotely from the site of inflammation by transferring mitochondria to sensory neurons. During resolution of inflammatory pain in mice, M2-like macrophages infiltrate the dorsal root ganglia that contain the somata of sensory neurons, concurrent with the recovery of oxidative phosphorylation in sensory neurons. The resolution of pain and the transfer of mitochondria requires expression of CD200 receptor (CD200R) on macrophages and the non-canonical CD200R-ligand iSec1 on sensory neurons. Our data reveal a novel mechanism for active resolution of inflammatory pain.
KW - Animals
KW - Ganglia, Spinal/metabolism
KW - Humans
KW - Macrophages/metabolism
KW - Mice
KW - Mitochondria
KW - Pain/metabolism
KW - Sensory Receptor Cells/metabolism
U2 - https://doi.org/10.1016/j.neuron.2021.11.020
DO - https://doi.org/10.1016/j.neuron.2021.11.020
M3 - Article
C2 - 34921782
SN - 0896-6273
VL - 110
SP - 613-626.e9
JO - Neuron
JF - Neuron
IS - 4
ER -