  Rheumatoid arthritis-associated joint pain is frequently observed independent
of disease activity, suggesting unidentified pain mechanisms. We demonstrate
that antibodies binding to cartilage, specific for collagen type II (CII) or
cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity
in mice, uncoupled from visual, histological and molecular indications of
inflammation. Cartilage antibody-induced pain-like behavior does not depend on
complement activation or joint inflammation, but instead on tissue antigen
recognition and local immune complex (IC) formation. smFISH and IHC suggest
that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of
primary afferents. CII-ICs directly activate cultured WT but not FcR{\gamma}
chain-deficient DRG neurons. In line with this observation, CII-IC does not
induce mechanical hypersensitivity in FcR{\gamma} chain-deficient mice.
Furthermore, injection of CII antibodies does not generate pain-like behavior
in FcR{\gamma} chain-deficient mice or mice lacking activating Fc{\gamma}Rs in
neurons. In summary, this study defines functional coupling between
autoantibodies and pain transmission that may facilitate the development of new
disease-relevant pain therapeutics.
