Pain Medicine

Biography

Biography: Hee-Jeong Im Sampen

Abstract

A key clinical paradox in osteoarthritis (OA), a prevalent age-related joint disorder characterized by cartilage degeneration and debilitating pain, is that the severity of joint pain doesn’t strictly correlate with radiographic and histological defects in joint tissues. Here, we determined whether protein kinase CPKCa key mediator of cartilage degeneration, is critical to the mechanism by which OA develops from an asymptomatic joint-degenerative condition to a painful disease. OA was induced in 10-week-old PKCnull (PKC) and wild type (WT) mice by destabilization of the medial meniscus (DMM) followed by comprehensive examination of the histology, molecular pathways, and knee-pain-related-behaviors in mice, and comparisons with human biopsies. In the DMM model, the loss of PKC expression prevented cartilage degeneration, but exacerbated OA-associated hyperalgesia. Cartilage preservation corresponded with reduced levels of inflammatory cytokines and of cartilage-degrading enzymes in the joints of PKCdeficient DMM mice. Hyperalgesia was associated with stimulation of nerve growth factor (NGF) by fibroblast-like synovial cells and with increased synovial angiogenesis. Results from tissue specimens of from symptomatic OA patients strikingly resembled our findings from the OA animal model. In PKC null mice, increases in sensory neuron distribution in knee OA synovium and activation of the NGF-tropomyosin receptor kinase (TrkA) axis in innervating dorsal root ganglia were highly correlated with knee OA hyperalgesia. Increased distribution of synovial sensory neurons in the joints, and augmentation of NGF/TrkA signaling, causes OA hyperalgesia independently of cartilage preservation.