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TitleNeuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases.
Publication TypeJournal Article
Year of Publication2020
AuthorsMailhot, Benoit, Marine Christin, Nicolas Tessandier, Chaudy Sotoudeh, Floriane Bretheau, Roxanne Turmel, Ève Pellerin, Feng Wang, Cyril Bories, Charles Joly-Beauparlant, Yves De Koninck, Arnaud Droit, Francesca Cicchetti, Grégory Scherrer, Eric Boilard, Reza Sharif-Naeini, and Steve Lacroix
JournalJ Exp Med
Volume217
Issue9
Date Published2020 Sep 07
ISSN1540-9538
Abstract

Chronic pain is a major comorbidity of chronic inflammatory diseases. Here, we report that the cytokine IL-1β, which is abundantly produced during multiple sclerosis (MS), arthritis (RA), and osteoarthritis (OA) both in humans and in animal models, drives pain associated with these diseases. We found that the type 1 IL-1 receptor (IL-1R1) is highly expressed in the mouse and human by a subpopulation of TRPV1+ dorsal root ganglion neurons specialized in detecting painful stimuli, termed nociceptors. Strikingly, deletion of the Il1r1 gene specifically in TRPV1+ nociceptors prevented the development of mechanical allodynia without affecting clinical signs and disease progression in mice with experimental autoimmune encephalomyelitis and K/BxN serum transfer-induced RA. Conditional restoration of IL-1R1 expression in nociceptors of IL-1R1-knockout mice induced pain behavior but did not affect joint damage in monosodium iodoacetate-induced OA. Collectively, these data reveal that neuronal IL-1R1 signaling mediates pain, uncovering the potential benefit of anti-IL-1 therapies for pain management in patients with chronic inflammatory diseases.

DOI10.1084/jem.20191430
Alternate JournalJ Exp Med
PubMed ID32573694
PubMed Central IDPMC7478735
Grant ListR01 DA044481 / DA / NIDA NIH HHS / United States
R01 NS106301 / NS / NINDS NIH HHS / United States