Transcutaneous vagal nerve stimulation improves post-traumatic osteoarthritis pain in mice

Vagus nerve stimulation (VNS) has been shown to improve chronic pain, including fibromyalgia, migraine headaches, and gastrointestinal pain, as well as inflammation in RA. Here, we investigated the efficacy of transcutaneous VNS (tVNS) in providing pain relief in a mouse model of post-traumatic osteoarthritis (PTOA). Destabilization of the medial meniscus (DMM) surgery was performed in 16-wk-old female and male mice. Beginning at 4 wk post-injury, mice were randomized to receive tVNS (10 min daily, 5 d per wk) delivered via the tragus of the ear or sham stimulation for 8 wk. Mechanical hyperalgesia, as measured using an algometer, and weight distribution were monitored at 3 time points: (1) pre-VNS, (2) 4-wk treatment, and (3) 8-wk treatment (end point of the study). Compared to the sham treatment, 4 wk of tVNS reduced mechanical hyperalgesia in female mice, and 8 wk of tVNS improved weight-bearing in male and female mice. tVNS altered serum pro-inflammatory cytokine and chemokine levels in a sex-dependent manner. Eight weeks of tVNS improved the lateral femur compartment of the DMM-affected joints in males. Our results reveal that tVNS improves PTOA-related pain and suppresses pro-inflammatory cytokine production, making it a promising, non-addictive intervention for chronic OA pain.