2022 Jan 27
doi: 10.1097/j.pain.0000000000002596. Online ahead of print.

Florian Jacquot Spiro KhouryBonnie LabrumKévin DelanoeLudivine PidouxJulie BarbierLauriane DelayAgathe BayleYoussef AissouniDavid A BarriereKim KultimaEva FreyhultAnders HugoEva KosekAisha S AhmedAlexandra JurczakEric LinguegliaCamilla I SvenssonVéronique BreuilThierry FerreiraFabien MarchandEmmanuel Deval


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.

Lysophosphatidylcholine 16: 0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3