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Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain

Oggero, Silvia; Cecconello, Chiara; Silva, Rita; Zeboudj, Lynda; Sideris-Lampretsas, George; Perretti, Mauro; Malcangio, Marzia; (2022) Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain. Brain, Behavior, and Immunity , 106 pp. 289-306. 10.1016/j.bbi.2022.09.008. Green open access

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Abstract

Pain is a persistent symptom of Rheumatoid Arthritis, and the K/BxN serum transfer model recapitulates both association and dissociation between pain and joint inflammation in RA. Furthermore, this model features monocyte/macrophage infiltration in joints and lumbar dorsal root ganglia (DRG), where these immune cells are close to nociceptive neurons. We focussed on CX3CR1-monocyte/macrophage trafficking and show that at peak paw swelling associated with nociception, CX3CR1 deletion altered neither swelling nor macrophage infiltration/phenotype in paws. However, acute nociception and DRG non-classical monocyte numbers were reduced in CX3CR1GFP/GFP (KO) compared to CX3CR1+/GFP (WT). Nociception that persisted despite swelling had resolved was attenuated in KO and correlated with DRG macrophages displaying M2-like phenotype. Still in the DRG, neurons up-regulated neuropeptide CGRP and olcegepant treatment reduced acute swelling, nociception, and leukocyte infiltration in paws and DRG. We delineate in-vitro a signalling pathway showing that CGRP liberates the CX3CR1 ligand fractalkine (FKN) from endothelium, and in bone marrow-derived macrophages, FKN promotes activation of intracellular kinases, polarisation towards M1-like phenotype and release of pro-nociceptive IL-6. These data implicate non-classical CX3CR1-expressing monocyte and macrophage recruitment into the DRG in initiation and maintenance of arthritis pain.

Type: Article
Title: Dorsal root ganglia CX3CR1 expressing monocytes/macrophages contribute to arthritis pain
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbi.2022.09.008
Publisher version: https://doi.org/10.1016/j.bbi.2022.09.008
Language: English
Additional information: © 2022 The Author(s). Published by Elsevier Inc. under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Macrophages, Monocytes, Arthritis, Fractalkine, CGRP, Pain
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10166056
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