Vagus nerve stimulation: A new bioelectronics approach to treat rheumatoid arthritis?

Abstract

There has been a marked improvement in the treatment of rheumatoid arthritis (RA), but most patients do not achieve disease remission. Therefore, there is still a need for new treatments. By screening an adenoviral short hairpin RNA library, we discovered that knockdown of the nicotinic acetylcholine receptor type 7 (α7nAChR) in RA fibroblast-like synoviocytes results in an increased production of mediators of inflammation and degradation. The α7nAChR is intimately involved in the cholinergic anti-inflammatory pathway (CAP). This led us to study the effects of α7nAChR activation in an animal model of RA, and we could show that this resulted in reduced arthritis activity. Accordingly, stimulation of the CAP by vagus nerve stimulation improved experimental arthritis. Conversely, we found aggravation of arthritis activity after unilateral cervical vagotomy as well as in α7nAChR-knockout mice. Together, these data provided the basis for exploration of vagus nerve stimulation in RA patients as a novel anti-inflammatory approach.

Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes

“…Judging by the creatinine level, renal histology, and other criteria 24 hours after renal ischemia, the protective effect of US and VNS is comparable in mice. In clinical trials to assess the benefit of VNS in RA, stimulation parameters such as current, pulse width, and frequency and duration of stimulation can be adjusted based on the effects and symptoms (30). We have not tried to optimize these parameters in the present study and may not have produced the maximum renal protection possible via VNS.…”

Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection

“…The cholinergic anti-inflammatory pathway was proven to be effective not only in sepsis [102], but also in a wide plethora of diseases with a strong inflammatory component like ischemia/ reperfusion [105][106][107], rheumatoid arthritis [108,109] or pancreatitis [110,111]. The selective a7 nAChR agonist GTS-21 [3-(2,4-dimethoxybenzylidene) anabaseine], initially developed for the treatment of AD [112,113], has been shown as a strong modulator of inflammation.…”

Cholinergic modulation of the immune system presents new approaches for treating inflammation

“…Collectively, this work provides strong evidence that therapeutic responses can be evoked in experimental arthritis by direct stimulation of α7 receptors or by activating the vagal anti-inflammatory pathway. Potential targets within the inflamed joints include macrophages and fibroblast-like synoviocytes that express α7 receptors (Koopman et al, 2014).…”