Published 2022
| Version v1
Journal article
Lysophosphatidylcholine 16:0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3
Creators
- Jacquot, Florian
- Khoury, Spiro
- Labrum, Bonnie
- Delanoe, Kévin
- Pidoux, Ludivine
- Barbier, Julie
- Delay, Lauriane
- Bayle, Agathe
- Aissouni, Youssef
- Barriere, David
- Kultima, Kim
- Freyhult, Eva
- Hugo, Anders
- Kosek, Eva
- Ahmed, Aisha
- Jurczak, Alexandra
- Lingueglia, Eric
- Svensson, Camilla
- Breuil, Véronique
- Ferreira, Thierry
- Marchand, Fabien
- Deval, Emmanuel
Contributors
Others:
- Neuro-Dol (Neuro-Dol) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
- Lipotoxicity and Channelopathies - ConicMeds (LitCh) ; Signalisation et Transports Ioniques Membranaires (STIM) ; Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)
- Department and FHU InovPain, Université Côte d'Azur, University Hospital of Nice, Nice, France.
- Institut de pharmacologie moléculaire et cellulaire (IPMC) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Uppsala University
- Department of Neuroscience, Karolinska institutet
- Department of Surgical Sciences [Uppsala, Sweden] ; Uppsala University
- Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
- Karolinska Institutet [Stockholm]
- Hôpital Pasteur [Nice] (CHU)
- ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011)
- ANR-17-CE16-0018,JOINT-PAIN,Douleur articulaire chronique : vers de nouvelles cibles moléculaires.(2017)
Description
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.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal.science/hal-04327490
- URN
- urn:oai:HAL:hal-04327490v1
Origin repository
- Origin repository
- UNICA