| First Author | Wang L | Year | 2019 |
| Journal | J Clin Invest | Volume | 129 |
| Issue | 9 | Pages | 3754-3769 |
| PubMed ID | 31211699 | Mgi Jnum | J:295245 |
| Mgi Id | MGI:6453664 | Doi | 10.1172/JCI128010 |
| Citation | Wang L, et al. (2019) Neuronal FcgammaRI mediates acute and chronic joint pain. J Clin Invest 129(9):3754-3769 |
| abstractText | 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 FcgammaRI, an immune receptor for IgG immune complex (IgG-IC), is expressed in a subpopulation of joint sensory neurons and that, under naive conditions, FcgammaRI 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, FcgammaRI 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 FcgammaRI 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 FcgammaRI merits consideration as a target for treating RA pain. |
