Lysophosphatidyl-choline 16:0 mediates persistent joint pain through Acid-Sensing Ion Channel 3: preclinical and clinical evidences

Florian Jacquot , Spiro Khoury , Bonnie Labrum , Kevin Delanoe , Ludivine Pidoux , Julie Barbier , Lauriane Delay , Agathe Bayle , Youssef Aissouni , David Barriere , Kim Kultima , Eva Freyhult , Anders Hugo , Eva Kosek , Aisha Ahmed , Alexandra Jurczak , Eric Lingueglia , Camilla Svensson , Veronique Breuil , Thierry Ferreira , Fabien Marchand , Emmanuel Deval (1)

1 IPMC - Institut de pharmacologie moléculaire et cellulaire

Rheumatic diseases are often associated to debilitating chronic joint pain, which remains difficult to treat and requires new therapeutic strategies. Here, we describe increased content of lysophosphatidyl-choline (LPC) 16:0 in the knee synovial fluids of two independent cohorts of patients with painful joint diseases. If LPC16:0 levels correlated with pain in patients with osteoarthritis (OA), they do not appear to be the hallmark of a particular joint disease. We found that intra-articular injections of LPC16:0 in mouse produce chronic pain and anxiety-like behaviors in both males and females with no apparent inflammation, peripheral nerve sprouting and damage, nor bone alterations. LPC16:0-induced persistent pain state is dependent on peripheral Acid-Sensing Ion Channel 3 (ASIC3), ultimately leading to central sensitization. LPC16:0 and ASIC3 thus appear as key players of chronic joint pain with potential implications in OA and possibly across others rheumatic diseases.

Domaines: Sciences du Vivant [q-bio]; Neurosciences [q-bio.NC]; Neurobiologie; Pharmacologie

Florian Jacquot, Spiro Khoury, Bonnie Labrum, Kevin Delanoe, Ludivine Pidoux, et al.. Lysophosphatidyl-choline 16:0 mediates persistent joint pain through Acid-Sensing Ion Channel 3: preclinical and clinical evidences. 2021. ⟨hal-03187657⟩