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

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Jacquot, Florian | Khoury, Spiro | Labrum, Bonnie | Delanoe, Kevin | 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, Veronique | Ferreira, Thierry | Marchand, Fabien | Deval, Emmanuel

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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.

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