Gowler PRW, et al. - Using clinical samples and animal models, researchers sought to investigate the potential contribution of knee joint brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signalling to chronic osteoarthritis (OA) pain. Knee synovia from OA patients (16 women, 14 men, median age 67 years [interquartile range: 61-73]) exhibited the presence of brain-derived neurotrophic factor and TrkB mRNA and protein. mRNA expression of NTRK2 (TrkB) was noted to have a significant positive correlation with the proinflammatory chemokine fractalkine in the OA synovia. Determination of the effects of peripheral BDNF injection, vs sequestering endogenous BDNF with TrkB-Fc chimera, on established pain behavior was done employing the surgical medial meniscal transection (MNX) model and the chemical monosodium iodoacetate (MIA) model of OA pain in male rats. In MIA rats, intra-articular injection of BDNF expanded established OA pain behavior but in controls, it had no effect. In both models of OA pain, intra-articular injection of the TrkB-Fc chimera acutely reversed pain behavior to a similar extent, compared with vehicle treatment. Findings suggest that peripheral knee joint BDNF/TrkB signaling contribute to the maintenance of chronic OA joint pain supporting further inquiry of the therapeutic potential of this target.