PT  - JOURNAL ARTICLE
AU  - Ramin Raoof
AU  - Michiel van der Vlist
AU  - Hanneke L.D.M. Willemen
AU  - Judith Prado
AU  - Sabine Versteeg
AU  - Martijn Vos
AU  - Roeland Lockhorst
AU  - R. Jeroen Pasterkamp
AU  - William Khoury-Hanold
AU  - Linde Meyaard
AU  - Niels Eijkelkamp
TI  - Macrophages transfer mitochondria to sensory neurons to resolve inflammatory pain
AID  - 10.1101/2020.02.12.940445
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.12.940445
4099  - http://biorxiv.org/content/early/2020/02/13/2020.02.12.940445.short
4100  - http://biorxiv.org/content/early/2020/02/13/2020.02.12.940445.full
AB  - The current paradigm states that inflammatory pain passively resolves following the cessation of the inflammatory insult. Yet, in a substantial proportion of patients with inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, spontaneous or treatment-induced resolution of inflammation is not sufficient to resolve pain, resulting in chronic pain1–5. Mechanistic insight as 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. To resolve pain, macrophages transfer mitochondria to sensory neurons. This transfer 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 and suggests a new direction for treatment of chronic pain.