Neuromodulation as a Potential Disease-Modifying Therapy for Osteoarthritis Author: Carlos J Cruz1,2, L Savannah Dewberry1, Kevin J Otto1,3,4,5,6, Kyle D Allen7,8,9 Affiliation: <sup>1</sup> J. Crayton Pruitt Family Department of Biomedical Engineering, Biomedical Sciences Building, University of Florida, 1275 Center Drive, Gainesville, FL, 32611, USA. <sup>2</sup> Pain Research and Intervention Center of Excellence, Gainesville, FL, USA. <sup>3</sup> Department of Materials Science and Engineering, University of Florida, Gainesville, FL, USA. <sup>4</sup> Department of Neurology, University of Florida, Gainesville, FL, USA. <sup>5</sup> Department of Electrical and Computer Engineering, University of Florida, Gainesville, FL, USA. <sup>6</sup> Department of Neuroscience, University of Florida, Gainesville, FL, USA. <sup>7</sup> J. Crayton Pruitt Family Department of Biomedical Engineering, Biomedical Sciences Building, University of Florida, 1275 Center Drive, Gainesville, FL, 32611, USA. kyle.allen@bme.ufl.edu. <sup>8</sup> Pain Research and Intervention Center of Excellence, Gainesville, FL, USA. kyle.allen@bme.ufl.edu. <sup>9</sup> Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville, FL, USA. kyle.allen@bme.ufl.edu. Conference/Journal: Curr Rheumatol Rep Date published: 2022 Nov 26 Other: Special Notes: doi: 10.1007/s11926-022-01094-2. , Word Count: 184 Purpose of review: The following review discusses the therapeutic potential of targeting the autonomic nervous system (ANS) for osteoarthritis (OA) treatment and encourages the field to consider the candidacy of bioelectronic medicine as a novel OA treatment strategy. Recent findings: The study of OA pathogenesis has focused on changes occurring at the joint level. As such, treatments for OA have been aimed at the local joint environment, intending to resolve local inflammation and decrease pain. However, OA pathogenesis has shown to be more than joint wear and tear. Specifically, OA-related peripheral and central sensitization can prompt neuroplastic changes in the nervous system beyond the articular joint. These neuroplastic changes may alter physiologic systems, like the neuroimmune axis. In this way, OA and related comorbidities may share roots in the form of altered neuroimmune communication and autonomic dysfunction. ANS modulation may be able to modify OA pathogenesis or reduce the impact of OA comorbidities. Moreover, blocking chronic nociceptive drive from the joint may help to prevent maladaptive nervous system plasticity in OA. Keywords: Neuroimmune axis; Osteoarthritis; Vagus nerve stimulation. PMID: 36435890 DOI: 10.1007/s11926-022-01094-2