Transcutaneous Vagus Nerve Stimulation Reduces Pain and OA Progression in Mouse Models of Post-Traumatic Osteoarthritis

Currently, there are no disease-modifying osteoarthritis (OA) drugs (DMOAD) to prevent OA progression and there are limitations on pain relieving therapeutics. Vagus nerve stimulation (VNS) delivered by an implantable device is FDA-approved for refractory epilepsy and severe depression. Here, we investigated the efficacy of transcutaneous VNS (tVNS) for preventing OA progression and providing pain relief in two mouse models of post-traumatic OA (PTOA): the surgical destabilized medial meniscus (DMM) and the non-surgical forced tibial compression anterior cruciate ligament rupture (ACLR). Here, we show that 2 weeks of tVNS significantly reduced histological OA scores in male and female mice after ACLR compared to sham stimulation. In female, but not male, mice, tVNS reduced hyperalgesia and mechanical allodynia. In the slower DMM model, 8 weeks of tVNS improved weight bearing in male and female mice, but only female mice had improved hyperalgesia. Male mice had lower OA histological scores. Serum proinflammatory cytokines were significantly reduced by tVNS in both models but differed by gender and model. Overall, these results provide strong pre-clinical evidence that tVNS reduces OA progression, improves pain, and suppresses pro-inflammatory cytokines, making it a promising DMOAD.