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Macrophage to neuron communication via extracellular vesicles in neuropathic pain conditions

Picco, Francesca; Zeboudj, Lynda; Oggero, Silvia; Prato, Vincenzo; Burgoyne, Thomas; Gamper, Nikita; Malcangio, Marzia; (2025) Macrophage to neuron communication via extracellular vesicles in neuropathic pain conditions. Heliyon , 11 (1) , Article e41268. 10.1016/j.heliyon.2024.e41268. Green open access

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Abstract

Neuropathic pain following peripheral nerve injury results from maladaptive changes in neurons and immune cells contribution to mechanisms underlying chronic pain. Specifically, in dorsal root ganglia (DRG), sensory neuron cell bodies release extracellular vesicles (EVs) which promote pro-inflammatory macrophage accumulation that facilitates nociceptive signalling. Here, we show that macrophages shuttle EVs to neurons. Indeed, bone marrow-derived macrophages (BMDMs) release EVs containing microRNA-155 (miR-155) which are taken up by cultured sensory neurons. EV-mediated transfer of miR-155 suppresses phosphatase Ship1 expression and increases cytokine interleukin-6 (IL-6) contents. Intrathecal-injected BMDM-derived EVs accumulate in lumbar DRG and EVs containing miR-155 antagomir result in Ship1 upregulation, Il6 downregulation in neurons in concomitance to attenuation of neuropathic mechanical hypersensitivity. These data suggest that, under neuropathic conditions, pro-inflammatory macrophages shuttle EV-containing miR-155 to neurons and contribute to the expression of pronociceptive IL-6 in DRG.

Type: Article
Title: Macrophage to neuron communication via extracellular vesicles in neuropathic pain conditions
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.heliyon.2024.e41268
Publisher version: https://doi.org/10.1016/j.heliyon.2024.e41268
Language: English
Additional information: © 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Neuropathic pain, DRG neurons, Macrophages, Extracellular vesicles, microRNAs, Cytokines
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10202807
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