Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 23, 2020
- Source ID
- 10.1084/jem.20191430
Entities
People
- Arnaud Droit
- Benoit Mailhot
- Charles Joly-beauparlant
- Chaudy Sotoudeh
- Cyril Bories
- Eric Boilard
- Feng Wang
- Floriane Bretheau
- Francesca Cicchetti
- Gregory Scherrer
- Marine Christin
- Nicolas Tessandier
- Reza Sharif-Naeini
- Roxanne Turmel
- Steve Lacroix
- Yves De Koninck
- Ève Pellerin
Organizations
- Arthritis Society
- CHUQ Foundation
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec Santé
- Laval University
- MS Walk
- McGill University
- National Institutes of Health
- Natural Sciences and Engineering Research Council
- New York Stem Cell Foundation
- Stanford University
- United States Department of Defense
- University of North Carolina
- University of North Carolina at Chapel Hill