Analysis of receptor localization in the central nervous system using in vitro and in vivo receptor autoradiography

Quantitative receptor autoradiography methods have been widely used over the last three decades to study the distribution and physiological role of a receptor in various tissues. This review provides an overview of in vivo and in vitro receptor autoradiography methods and their advantages as well as disadvantages in the study of receptors in the central nervous system. Comparison with immunohistochemical and in situ hybridization methods is also highlighted in relation to the study of a given receptor in the nervous sytem

Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons

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