title: 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.
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: Koopman
authors.affiliation: Department of Neurosurgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: P R
authors.initials: PR
authors.lastname: Schuurman
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Vervoordeldonk
authors.affiliation: Department of Clinical Immunology and Rheumatology, Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; GlaxoSmithKline, Stevenage, United Kingdom; University of Cambridge, Cambridge, United Kingdom. Electronic address: p.p.tak@amc.uva.nl.
authors.forename: P P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D055536:Vagus Nerve Stimulation / Q000379:methods*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Cholinergic anti-inflammatory pathway; Rheumatoid arthritis; Vagus nerve stimulation