New Insights into Molecular and Functional Pathways Reveal Novel Mechanism-based Approaches for Targeting Osteoarthritis Pain

Anne-Marie Malfait, MD, PhD, Rush University

Pain arising as a symptom of osteoarthritis is a formidable problem worldwide. NSAIDs and opioids are widely used, but these drugs generally do not provide sustained pain relief and they have considerable side effects that make their chronic use problematic. Newer approaches in clinical trials, such as the sequestration of the neurotrophin, nerve growth factor (NGF), are promising but are associated with ill-understood side effects such as rapidly progressive osteoarthritis. A better understanding of the molecular and cellular basis of osteoarthritis pain should help to discover new therapeutic targets for analgesic drug development, and further elucidate the relationship between joint damage and pain. This problem can now be tackled by a variety of techniques that bring together the disciplines of arthritis research and neuroscience – for example, the development of clinically relevant behavioral tests for osteoarthritis pain in relevant animal models, single cell transcriptomics designed to elucidate the molecular characteristics of populations of joint nociceptors, genetic techniques that allow the identification of neuronal subsets through the expression of fluorescent markers enabling their anatomical characterization assisted by clearing methods, in vivo calcium imaging and related methods for assessing the physiological functioning of relevant pain pathways in real time, and molecular characterization in human neuronal tissues. New insights from such cross-disciplinary studies are expected to reveal novel mechanism-based, tailored strategies for addressing osteoarthritis.