Evaluating The Joint-Level, Systemic, And Symptomatic Consequences Of Low Vagal Tone In A Rat Model Of Knee Osteoarthritis

Purpose: Recently, characterization of osteoarthritis (OA) pathophysiology has extended beyond the joint, with an emphasis on understanding the impacts of multi-organ system crosstalk on overall joint health. Crosstalk between the joint and other physiologic systems is facilitated by the nervous system, which becomes sensitized in OA (e.g., peripheral and central sensitization). Moreover, nervous system sensitization can prompt neuroplastic shifts to neuroimmune axes which are regulated by the autonomic nervous system (ANS). Specifically, the ANS consists of two branches — the sympathetic and parasympathetic nervous system — which work in concert to regulate neuroimmune health via the hypothalamic-pituitary-adrenal axis, cholinergic/splanchnic anti-inflammatory pathways, and gut microbiome diversity. For example, functional shifts in the parasympathetic component (i.e., vagal tone) of the ANS have been associated with OA comorbidities (e.g., diabetes, hypertension, obesity), where a greater risk and/or incidence of OA is shown alongside ANS dysfunction; thus, functional shifts to the ANS might contribute to a decline in overall joint health. Therefore, determining whether low vagal tone and OA are related could uncover new treatment opportunities for OA, such as vagus nerve stimulation. Here, we evaluated whether low vagal tone contributes to OA pathogenesis, hypothesizing that reducing vagal tone via vagotomy will accelerate OA-related symptoms and joint-level changes in a rat model of knee OA.