Title | Neuronal interleukin-1 receptors mediate pain in chronic inflammatory diseases. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Mailhot, 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 |
Journal | J Exp Med |
Volume | 217 |
Issue | 9 |
Date Published | 2020 Sep 07 |
ISSN | 1540-9538 |
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. |
DOI | 10.1084/jem.20191430 |
Alternate Journal | J Exp Med |
PubMed ID | 32573694 |
PubMed Central ID | PMC7478735 |
Grant List | R01 DA044481 / DA / NIDA NIH HHS / United States R01 NS106301 / NS / NINDS NIH HHS / United States |