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.
Preview |
PDF
1-s2.0-S088915912200383X-main.pdf - Published Version Download (16MB) | Preview |
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.
Archive Staff Only
 |
View Item |
