Advances in Osteoarthritis Pain Mechanisms

The number of people suffering from osteoarthritis (OA) pain have increased dramatically over the last decades. Emerging data from clinical trials, imaging studies, RNA sequencing of diseased joint tissues, human genetics, surgically and chemically-induced OA-like animal pain models, the discovery of senescence associated secretory cell phenotype and novel genetic and pharmacological tools provides new hope in understanding of OA pain driver mechanisms and eventual successful treatment of pain. A finding that joint replacement surgery provides pain relief in most OA pain patients suggests peripheral genesis of OA pain. Further, clinical findings in imaging studies show that subchondral bone lesions and bone cysts correlate with weight bearing pain. A recent discovery of abnormal sensory nerve innervation, increased number of osteoclasts, fibroblasts, mast cells and macrophages in painful OA patient subchondral bone lesions and synovium suggests that non-neuronal-sensory neuron interaction play a key role in OA pain transduction. The goal of the research topic is to understand in more detail the role of sensory neurons, osteoclasts, fibroblasts and other cells in microenvironment of subchondral bone lesions and synovium in the genesis and maintenance of OA pain. Further, aging and obesity are established risk factors for the development of OA pain. Obesity is recently found to promote cellular senescence. Is there evidence for a senescence associated secretory osteoclast phenotype in OA patient joint tissues and OA animal models? Mature and functional osteoclasts and other myeloid cells from joint tissues are difficult to isolate to grow in a dish. Therefore, most in vitro studies use bone-marrow-derived precursor cells and differentiated cells from plasma. How well such cells replicate disease-associated phenotype in vitro? Recent study shows that nociceptor sprouting starts early in synovium and subchondral bone in OA in vivo disease models and correlates with joint pathology. Further, in vivo studies suggest that injured ATF3 positive sensory neurons may contribute to OA-like pain. Do non-neuronal cells in subchondral bone and synovium release NGF-like growth factors that stimulate neuronal sprouting but also factors that injure neurons? Topic editors: Qimiao Hu, Ari-Pekka Koivisto, Dasheng Lin Source: https://www.frontiersin.org/research-topics/70052/advances-in-osteoarthritis-pain-mechanisms