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Papers of the Week

Papers: 18 Dec 2021 - 24 Dec 2021

Human Studies, Pharmacology/Drug Development

2021 Nov 19


Editor's Pick

Antibody-induced pain-like behavior and bone erosion: links to subclinical inflammation, osteoclast activity and ASIC3-dependent sensitization.


Jurczak A, Delay L, Barbier J, Simon N, Krock E, Sandor K, Agalave NM, Rudjito R, Wigerblad G, Rogóż K, Briat A, Miot-Noirault E, Martinez-Martinez A, Brömme D, Grönwall C, Malmström V, Klareskog L, Khoury S, Ferreira T, Labrum B, et al.
Pain. 2021 Nov 19.
PMID: 34924556.


Several bone conditions e.g., bone cancer, osteoporosis and rheumatoid arthritis (RA) are associated with a risk of developing persistent pain. Increased osteoclast activity is often the hallmark of these bony pathologies and leads not only to bone remodeling but is also a source of pronociceptive factors that sensitize the bone-innervating nociceptors. Although historically bone loss in RA has been thought to be a consequence of inflammation, both bone erosion and pain can occur years before the symptom onset. Here we have addressed the disconnection between inflammation, pain and bone erosion by using a combination of two monoclonal antibodies isolated from B-cells of RA patients. We have found that mice injected with B02/B09 mAbs developed a long-lasting mechanical hypersensitivity which was accompanied by bone erosion in the absence of joint edema or synovitis. Intriguingly, we have noted a lack of analgesic effect of naproxen and a moderate elevation of few inflammatory factors in the ankle joints suggesting that B02/B09-induced pain-like behavior does not depend on inflammatory processes. In contrast, we found that inhibiting osteoclast activity and ASIC3 signaling prevented the development of B02/B09-mediated mechanical hypersensitivity. Moreover, we have identified phospholipase A2 (sPLA2) and lysophospatidylcholine 16:0 as critical components of B02/B09-induced pain-like behavior and shown that treatment with sPLA2 inhibitor reversed B02/B09-induced mechanical hypersensitivity and bone erosion. Taken together, our study suggests a potential link between bone erosion and pain in a state of subclinical inflammation and offers a step forward in understanding the mechanisms of bone pain in diseases like RA.