Lysophosphatidylcholine 16:0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3. Issue 10 (27th October 2022)

• Record Type: Journal Article
• Authors: Jacquot, Florian; Khoury, Spiro; Labrum, Bonnie; Delanoe, Kévin; Pidoux, Ludivine; Barbier, Julie; Delay, Lauriane; Bayle, Agathe; Aissouni, Youssef; Barriere, David A.; Kultima, Kim; Freyhult, Eva; Hugo, Anders; Kosek, Eva; Ahmed, Aisha S.; Jurczak, Alexandra; Lingueglia, Eric; Svensson, Camilla I.; Breuil, Véronique; Ferreira, Thierry; Marchand, Fabien; Deval, Emmanuel
• Is Part Of: Pain. Volume 163:Issue 10(2022)
• Page Start: 1999
• Page End: 2013
• Publication Date: 2022-10-27
• Subjects: Chronic pain -- Joint -- Osteoarthritis -- Lysophosphatidylcholine -- Lipid -- Acid-sensing ion channels -- Sodium channels; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000002596
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Supplemental Digital Content is Available in the Text. A combination of clinical and preclinical data that support a role for the lysolipid LPC16:0 via acid-sensing ion channels 3 in chronic joint pain related to rheumatic diseases. Abstract: Rheumatic diseases are often associated to debilitating chronic pain, which remains difficult to treat and requires new therapeutic strategies. We had previously identified lysophosphatidylcholine (LPC) in the synovial fluids from few patients and shown its effect as a positive modulator of acid-sensing ion channel 3 (ASIC3) able to induce acute cutaneous pain in rodents. However, the possible involvement of LPC in chronic joint pain remained completely unknown. Here, we show, from 2 independent cohorts of patients with painful rheumatic diseases, that the synovial fluid levels of LPC are significantly elevated, especially the LPC16:0 species, compared with postmortem control subjects. Moreover, LPC16:0 levels correlated with pain outcomes in a cohort of osteoarthritis patients. However, LPC16:0 do not appear to be the hallmark of a particular joint disease because similar levels are found in the synovial fluids of a second cohort of patients with various rheumatic diseases. The mechanism of action was next explored by developing a pathology-derived rodent model. Intra-articular injections of LPC16:0 is a triggering factor of chronic joint pain in both male and female mice, ultimately leading to persistent pain and anxiety-like behaviors. All these effects are dependent on ASIC3 channels, which drive sufficient peripheral inputs to generate spinal sensitization processes. This study brings evidences from mouse and human supporting a role for LPC16:0 via ASIC3 channels in chronic pain arising from joints, with potential implications for pain management in osteoarthritis and possibly across other rheumatic diseases.