Electrical stimulation of the arterial splenic nerve has durable therapeutic efficacy on murine collagen-induced arthritis.

Abstract

Vagus nerve (VN) stimulation has anti-arthritic effects in animal models and in patients with rheumatoid arthritis (RA). However, VN stimulation may affect several physiological functions. The splenic nerve (SpN) has been implicated in VN-mediated immunomodulation. We tested the therapeutic efficacy of arterial SpN stimulation (SNS) on collagen-induced arthritis (CIA) in mice as a single treatment or in combination with etanercept or Jak inhibitor. SNS was evaluated in mice with CIA before or after disease onset and applied one or six times daily. Alternatively, mice were treated with etanercept or propranolol three times a week. SNS treatment of CIA mice before the onset of clinical symptoms prevented disease in a β1/β2-adrenoceptor-dependent manner. After SNS treatment, splenic inflammatory monocytes, B cells and autoantibody-secreting cells were reduced, as were serum levels of TNF and anti-collagen antibodies. When SNS was tested as a therapeutic modality in already diseased mice, clinical scores were significantly reduced compared to sham-treated animals. Importantly, the therapeutic efficacy of SNS was enhanced when combined with etanercept treatment. The results of this study suggest that SNS may have potent therapeutic anti-arthritogenic effects.