Lend an ear to fight arthritis?

Non-invasive vagus nerve stimulation shows promise for treatment of rheumatoid arthritis

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MANHASSET, N.Y.—Not all medicine consists of drugs or drug-like therapeutics such as gene-editing, as researchers recently showed with “bioelectronic medicine” studied as an effective treatment for rheumatoid arthritis (RA). Their findings were published in mid-April in Bioelectronic Medicine under the title “Investigational treatment of rheumatoid arthritis with a vibrotactile device applied to the external ear.”
Scientists at The Feinstein Institute for Medical Research—the research arm of Northwell Health, one of New York’s largest healthcare providers—collaborated with counterparts from Academic Medical Center at University of Amsterdam in the Netherlands to carry out a series of pilot clinical studies to assess the effect of a novel bioelectronic stimulation. The work isn’t in and of itself entirely new, as the authors note in the paper that “Positive pilot clinical trial results have been reported in patients with RA and Crohn’s disease treated with implanted stimulators that deliver electrical impulses to the cervical vagus nerve (Koopman et al. 2016; Bonaz et al. 2016).”
But what is different is the non-invasive nature of the more recent work by the Feinstein researchers and colleagues. Their recent work show that stimulation at the external ear improves disease symptoms in patients with RA. This is a potentially valuable area of discovery, as the signs and symptoms of RA are treated using synthetic and biological antirheumatic drugs that can not only result in side effects, but also have mixed effectiveness in RA patients.
In the recent pilot study, Dr. Sangeeta S. Chavan, a Feinstein Institute professor, and Meghan E. Addorisio tested the efficacy of non-invasive vagus nerve stimulation to reduce inflammation and improve disease severity in RA patients. They found that bioelectronic medicine treatment was effective in inhibiting the production of cytokines, proteins that mediate inflammation and reduce the inflammatory responses in patients with rheumatoid arthritis.
Or, as the authors of the paper put it much more comprehensively (and technically) in the paper’s introduction: “Recent studies revealed that innate and adaptive immunity are also controlled by neural reflex mechanisms (Chavan et al. 2017; Chavan and Tracey 2017; Pavlov et al. 2018). The vagus nerve-based inflammatory reflex is a physiological mechanism though which the vagus nerve signals regulate immune function (Borovikova et al. 2000; Andersson and Tracey 2012b; Tracey 2002). Molecular mediators of innate immunity activate the afferent signals in the vagus nerve which are transmitted to the brainstem that controls outgoing efferent signals in the vagus nerve. Efferent signals arising in the vagus nerve are then transmitted to the splenic nerve and synapse on splenic lymphocytes causing them to release acetylcholine, which binds the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages and monocytes (Chavan et al. 2017; Wang et al. 2003; Olofsson et al. 2012). Signal transduction induced by acetylcholine binding increases intracellular calcium, decreases nuclear translocation of NFκB, stabilizes mitochondrial membranes, and inhibits inflammasome activity. These events result in the reduction of the pro-inflammatory cytokines TNF, IL-1β, and IL-6 produced by the spleen (Olofsson et al. 2012). α7nAChR-mediated inhibition of TNF is dependent on CREB and c-FOS (Tarnawski et al. 2018).”
Said Chavan of the research: “Our primary objective was to observe if a non-invasive treatment using an external device will be effective in improving disease severity of rheumatoid arthritis that continues to plague more than one million across the country each year. We are pleased to observe that this novel bioelectronic treatment significantly reduces swelling and inflammation associated with RA.”

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