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

被引:77
作者
Koopman, F. A. [1 ]
Schuurman, P. R. [2 ]
Vervoordeldonk, M. J. [1 ]
Tak, P. P. [1 ,3 ,4 ]
机构
[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, Amsterdam Rheumatol & Immunol Ctr, NL-1100 DE Amsterdam, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Neurosurg, NL-1100 DE Amsterdam, Netherlands
[3] GlaxoSmithKline, Stevenage, Herts, England
[4] Univ Cambridge, Cambridge, England
来源
BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY | 2014年 / 28卷 / 04期
关键词
Rheumatoid arthritis; Cholinergic anti-inflammatory pathway; Vagus nerve stimulation; NICOTINIC ACETYLCHOLINE-RECEPTOR; HEART-RATE-VARIABILITY; CHOLINERGIC ANTIINFLAMMATORY PATHWAY; COLLAGEN-INDUCED ARTHRITIS; DISEASE-ACTIVITY; CIGARETTE-SMOKING; FUNCTIONAL STATUS; SYNOVIAL TISSUE; ALPHA-7; SUBUNIT; NEURAL SIGNALS;
D O I
10.1016/j.berh.2014.10.015
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 (alpha 7nAChR) in RA fibroblast-like synoviocytes results in an increased production of mediators of inflammation and degradation. The a7nAChR is intimately involved in the cholinergic anti-inflammatory pathway (CAP). This led us to study the effects of alpha 7nAChR 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 alpha 7nAChR-knockout mice. Together, these data provided the basis for exploration of vagus nerve stimulation in RA patients as a novel anti-inflammatory approach. (C) 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
引用
收藏
页码:625 / 635
页数:11
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