Background/Purpose: Osteoarthritis (OA) is the most common form of arthritis, affecting over 32.5 million US adults and characterized by pain, stiffness, swelling and functional disability. Currently, we have limited treatment option for effective OA pain management. Vagal nerve stimulation (VNS), FDA approved for treatment of epilepsy and depression, is an attractive treatment for OA pain as it activates a cholinergic anti-inflammatory pathway, driving the production of acetylcholine (Ach) in nerves and non-neuronal cells, and provides a strong systemic anti-inflammatory effect that reduces synovial inflammation and joint pain in mouse models of rheumatoid arthritis. We hypothesized that transcutaneous-VNS (tVNS) via tragus of the ear would reduce knee pain induced by surgical destabilizing of the medial meniscus (DMM) in mice.

Methods: At 16 weeks of age, DMM surgery was performed on one knee in both male (n=20) and female (n=19) C57BL6/J mice. Four weeks after DMM surgery, mice were randomly assigned to 10 minutes of tVNS treatment (VNS group) and 10 minutes of sham-VNS treatment with device attached to tragus but not turned on (SHAM group) for 5 days per week for 8 weeks. Pressure algometry and dynamic weight-bearing pain behavior were measured at 4, 8, and 12 weeks post-surgery. Knee joints for histologic OARSI grading and serum for multiplex cytokine analysis were collected at 12 weeks post-surgery.

Results: Compared to SHAM-VNS, tVNS improved algometer-induced pain at 4 weeks and weight-bearing at 8 weeks in female mice. Compared to SHAM-VNS, weight-bearing improvement was seen at 4 weeks in tVNS treated male mice. Compared to SHAM-VNS, tVNS-treated females had significantly lower levels of IFNγ (6.06 ±3.44 vs 2.53 ±1.41, p = 0.02), IL-5 (4.55 ± 2.43 vs 2.51 ± 0.96, p = 0.04), and IL-9 (8.16 ± 5.29 vs 2.58 ± 2.72, p = 0.008). Compared to SHAM-VNS, tVNS treated male mice had significantly decreased GM-CSF (26.46 ± 14.65 vs 12.55 ± 4.93, p = 0.037) and IL-2 (13.16 ± 29.21 vs 1.24 ± 0.52, p = 0.007); whereas MIP-1β (89.18 ± 43.02 vs 136.34 ± 90.18, p = 0.035) and IL-4 (2.90 ± 5.65 vs 4.36 ± 6.62, p-0.017) were significantly increased. Histological analysis of the knee is being investigated.

Conclusion: Our study indicates that tVNS improves pain in male and female mice after DMM surgery and suggests a role of IFN-γ, IL-5, IL-9, GM-CSF, IL-2, MIP-1β, and IL-4 in OA pain. tVNS may be a promising non-invasive treatment for OA pain.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/transcutaneous-vagal-nerve-stimulation-improves-destabilized-medial-meniscus-induced-osteoarthritis-pain-associated-with-significant-serum-biomarker-changes/