Exogenous artemin induces mechanical, heat, and cold hypersensitivity, and systemic intraperitoneal anti-artemin monoclonal antibody administration reverses this hypersensitivity and restores limb use in mice with MIA-induced OA-pain. We found the monoiodoacetate (MIA)-induced OA-pain in mice is associated with decreased limb use and hypersensitivity. Here, we use multiple approaches, including cellular, mouse genetic, immunological suppression in a mouse model of OA, and clinically relevant measures of sensitivity and limb use to explore the functional role of artemin/GFRα3 signaling in OA-pain. In previous work in naturally occurring OA-pain in dogs, we identified potential signaling molecules (artemin/GFRα3) that were upregulated. The lack of therapeutic options is partly due to a lack of understanding of clinically relevant underlying neural mechanisms of OA-pain. Therapeutic options are limited, and the available options are often associated with adverse effects. OA-pain limits limb use and mobility and is associated with widespread sensitivity. Osteoarthritis (OA) associated pain (OA-pain) is a significant global problem. 6Department of Anesthesiology, Center for Translational Pain Research, Duke University, Durham, NC, United States.5Thurston Arthritis Center, UNC School of Medicine, Chapel Hill, NC, United States.4Comparative Pain Research and Education Center, North Carolina State University, Raleigh, NC, United States.
3Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.2Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.1Translational Research in Pain Program, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.Laura Minnema 1†, Ankita Gupta 1,2†, Santosh K.