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Neuronal FcγRI mediates acute and chronic joint pain.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 2019 Jun 18; Vol. 129 (9), pp. 3754-3769. Date of Electronic Publication: 2019 Jun 18. - Publication Year :
- 2019
-
Abstract
- Although joint pain in rheumatoid arthritis (RA) is conventionally thought to result from inflammation, arthritis pain and joint inflammation are at least partially uncoupled. This suggests that additional pain mechanisms in RA remain to be explored. Here we show that FcγRI, an immune receptor for IgG immune complex (IgG-IC), is expressed in a subpopulation of joint sensory neurons and that, under naïve conditions, FcγRI crosslinking by IgG-IC directly activates the somata and peripheral terminals of these neurons to evoke acute joint hypernociception without obvious concurrent joint inflammation. These effects were diminished in both global and sensory neuron-specific Fcgr1 knockout mice. In murine models of inflammatory arthritis, FcγRI signaling was upregulated in joint sensory neurons. Acute blockade or global genetic deletion of Fcgr1 significantly attenuated arthritis pain and hyperactivity of joint sensory neurons without measurably altering joint inflammation. Conditional deletion of Fcgr1 in sensory neurons produced similar analgesic effects in these models. We therefore suggest that FcγRI expressed in sensory neurons contributes to arthritis pain independently of its functions in inflammatory cells. These findings expand our understanding of the immunosensory capabilities of sensory neurons and imply that neuronal FcγRI merits consideration as a target for treating RA pain.
- Subjects :
- Acute Pain metabolism
Animals
Antigen-Antibody Complex
Arthritis, Experimental immunology
Arthritis, Experimental physiopathology
Arthritis, Rheumatoid immunology
Chronic Pain metabolism
Cross-Linking Reagents pharmacology
Gene Deletion
Immunoglobulin G metabolism
Inflammation
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Sensory Receptor Cells metabolism
Arthralgia metabolism
Arthritis, Experimental metabolism
Neurons metabolism
Receptors, IgG metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1558-8238
- Volume :
- 129
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 31211699
- Full Text :
- https://doi.org/10.1172/JCI128010