Antibody-induced pain-like behavior and bone erosion: links to subclinical inflammation, osteoclast activity, and acid-sensing ion channel 3–dependent sensitization. Issue 8 (19th August 2022)

• Record Type: Journal Article
• Authors: Jurczak, Alexandra; Delay, Lauriane; Barbier, Julie; Simon, Nils; Krock, Emerson; Sandor, Katalin; Agalave, Nilesh M.; Rudjito, Resti; Wigerblad, Gustaf; Rogóż, Katarzyna; Briat, Arnaud; Miot-Noirault, Elisabeth; Martinez-Martinez, Arisai; Brömme, Dieter; Grönwall, Caroline; Malmström, Vivianne; Klareskog, Lars; Khoury, Spiro; Ferreira, Thierry; Labrum, Bonnie; Deval, Emmanuel; Jiménez-Andrade, Juan Miguel; Marchand, Fabien; Svensson, Camilla I.
• Is Part Of: Pain. Volume 163:Issue 8(2022)
• Page Start: 1542
• Page End: 1559
• Publication Date: 2022-08-19
• Subjects: Pain -- Osteoclasts -- Bone -- Autoantibodies -- Rheumatoid arthritis -- ASIC3 -- Lipids -- LPC -- sPLA2; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000002543
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Supplemental Digital Content is Available in the Text. Inhibiting osteoclast activity and acid-sensing ion channel 3 signaling prevents the development of autoantibody-mediated mechanical hypersensitivity, and increased lysophosphatidylcholine 16:0 and secretory phospholipase A2 contribute to sensitization in this model. Abstract: Several bone conditions, eg, 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 not only leads 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 believed 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 2 monoclonal antibodies isolated from B cells of patients with RA. We have found that mice injected with B02/B09 monoclonal antibodies (mAbs) developed a long-lasting mechanical hypersensitivity that 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. By contrast, we found that inhibiting osteoclast activity and acid-sensing ion channel 3 signaling prevented the development of B02/B09-mediated mechanical hypersensitivity. Moreover, we have identified secretory phospholipase A2 and lysophosphatidylcholine 16:0 as critical components of B02/B09-induced pain-like behavior and shown that treatment with a secretory phospholipase A2 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 such as RA.