A study published in PLoS ONE is perhaps the first to demonstrate that electrical neurostimulation of the vagus nerve reduces signs of inflammation and disease severity in the collagen-induced arthritis (CIA), a disease model of rheumatoid arthritis in rodents.
Nearly all neuroanatomical studies indicate that lymphoid organs such as the spleen, thymus or lymph nodes do not receive direct cholinergic/parasympathetic or vagal nerve innervation. Thus, it is not entirely clear how the vagus exerts immunomodulation. However, as electrical stimulation of the vagus nerve fails to attenuate serum TNF levels in splenectomized mice (cf. Van Der Zanden EP et al., Koopman FA et al.), it was suggested that the vagus nerve affects immune cells within the spleen indirectly via activation of sympathetic postganglionic neurons localized in the coeliac ganglia (see cover image, and, below, its source and legend). The vagus nerve, via these ganglia, may modulate the noradrenergic/sympathetic neural input to the spleen. This may include the release of catecholamines such as norepinephrine (noradrenaline), and via stimulation of adrenergic receptors, a subsequent inhibition of pro-inflammatory cytokine production.
In the PLoS ONE study, Y. Levine and colleagues, as part of an international research team from the US, UK and the Netherlands used neurostimulation delivered by implanted electrical vagus nerve stimulation cuff electrode, analogous to those now in clinical use for drug-resistant epilepsy (Beekwilder JP & Beems T, J Clin Neurophysiol, 2010, 27:130). In rats with autoimmune CIA this neurostimulation was related to reduction in ankle swelling, inflammation, pannus formation, cartilage damage and bone resorption. This was associated with reductions in IL-1β, IL-2, IL-6, IFN-γ and TNF systemic levels, not reaching statistical significance.
Thus, the study may justify testing of vagus nerve stimulation in human immune/inflammatory disorders, and/or suggest novel therapeutic strategies in patients with rheumatoid arthritis.