Can vagus nerve stimulation halt or ameliorate rheumatoid arthritis and lupus?

Abstract

Acetylcholine, the principal vagus neurotransmitter, inhibits inflammation by suppressing the production of proinflammatory cytokines through a mechanism dependent on the α7 nicotinic acetylcholine receptor subunit (alpha7nAChR) that explains why vagus nerve stimulation is anti-inflammatory in nature. Strong expression of alpha7nAChR in the synovium of rheumatoid arthritis and psoriatic arthritis patients was detected. Peripheral macrophages and synovial fibroblasts respond in vitro to specific alpha7nAChR cholinergic stimulation with potent inhibition of proinflammatory cytokines. Fibroblasts balance inflammatory mechanisms and arthritis development through feedback cholinergic stimulation by nearby immune cells. Collagen induced arthritis in alpha7nAChR (-/-) mice was significantly severe and showed increased synovial inflammation and joint destruction compared to the wild-type mice. Similar to vagal nerve stimulation and alpha7nAChR agonists, polyunsaturated fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also suppress inflammation. In view of their similar anti-inflammatory actions, it is proposed that vagal nerve stimulation, alpha7nAChR agonists and EPA and DHA may augment the formation of anti-inflammatory lipid molecules: lipoxins, resolvins, protectins and maresins. This implies that therapies directed at regulation of the cholinergic and alpha7nAChR mediated mechanisms and enhancing the formation of lipoxins, resolvins, protectins and maresins may halt and/or ameliorate rheumatoid arthritis, lupus and other rheumatological conditions.

Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids

“…These findings suggest that abnormalities of the cholinergic nervous system exist in autism. It is noteworthy that acetylcholine, the principal vagal neurotransmitter, has potent anti-inflammatory actions and suppresses the production of interleukin (IL)-6, tumor necrosis factor (TNF)-a, and high-mobility group box-1 [28][29][30]. This suggests that there could be a role for inflammatory pathways in the pathobiology of autism.…”

Presence of ChAT mRNA and a very marked α7nAChR immunoreaction in the synovial lining layer of the knee joint

“…Bruchfeld et al, 2010). Studies showing that nicotine can inhibit the TNF-alpha pathway for synoviocyes (Zhou et al, 2010), and that synovial fibroblasts respond in vitro to cholinergic stimulation (via the α7nAChR) with potent inhibition of proinflammatory cytokines (Das, 2011), favor a suggestion that cholinergic agonist treatment might be useful. In studies on collagen-induced arthritis for α7nAChR knockout mice, it has furthermore been shown that the absence of α7nAChR was associated with an aggravated arthritis (van Maanen et al, 2010).…”

Gas-Therapy in Rheumatoid Arthritis Treatment: When West Meets East – Actual Medical Concepts with Ancient World Ideas

“…Strong expression of nicotinic receptor in the synovium of RA patients was detected by Das [70]. Both peripheral macrophages and synovial fibroblasts respond to specific cholinergic stimulation with potent inhibition of proinflammatory cytokines.…”

“…It was proposed by Das [70] that vagal nerve stimulation, or nicotinic agonists may augment the formation of anti-inflammatory lipid molecules: lipoxins, resolvins, protectins and maresins. This implies that new therapies focused on directed regulation of the cholinergic mediated mechanisms and enhancing the formation of lipoxins, resolvins, protectins and maresins may halt and/or ameliorate RA [70]. It is very important to note, that electrical stimulation of the vagus nerve, ie.…”