Tyrosine kinase type A–specific signalling pathways are critical for mechanical allodynia development and bone alterations in a mouse model of rheumatoid arthritis - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Pain Année : 2022

Tyrosine kinase type A–specific signalling pathways are critical for mechanical allodynia development and bone alterations in a mouse model of rheumatoid arthritis

Résumé

Abstract Rheumatoid arthritis is frequently associated with chronic pain that still remains difficult to treat. Targeting nerve growth factor (NGF) seems very effective to reduce pain in at least osteoarthritis and chronic low back pain but leads to some potential adverse events. Our aim was to better understand the involvement of the intracellular signalling pathways activated by NGF through its specific tyrosine kinase type A (TrkA) receptor in the pathophysiology of rheumatoid arthritis using the complete Freund adjuvant model in our knock-in TrkA/C mice. Our multimodal study demonstrated that knock-in TrkA/C mice exhibited a specific decrease of mechanical allodynia, weight-bearing deficit, peptidergic (CGRP+) and sympathetic (TH+) peripheral nerve sprouting in the joints, a reduction in osteoclast activity and bone resorption markers, and a decrease of CD68-positive cells in the joint with no apparent changes in joint inflammation compared with wild-type mice after arthritis. Finally, transcriptomic analysis shows several differences in dorsal root ganglion mRNA expression of putative mechanotransducers, such as acid-sensing ionic channel 3 and TWIK-related arachidonic acid activated K+ channel, as well as intracellular pathways, such as c-Jun, in the joint or dorsal root ganglia. These results suggest that TrkA-specific intracellular signalling pathways are specifically involved in mechanical hypersensitivity and bone alterations after arthritis using TrkA/C mice.

Dates et versions

hal-04316536 , version 1 (30-11-2023)

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Lauriane Delay, Julie Barbier, Youssef Aissouni, Alexandra Jurczak, Ludivine Boudieu, et al.. Tyrosine kinase type A–specific signalling pathways are critical for mechanical allodynia development and bone alterations in a mouse model of rheumatoid arthritis. Pain, 2022, 163 (7), pp.e837-e849. ⟨10.1097/j.pain.0000000000002492⟩. ⟨hal-04316536⟩
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