Medical Research

Specific vagus nerve stimulation parameters alter serum cytokine levels in the absence of inflammation

Kristen Sparrow • November 12, 2021

Coastline is a fractal, so is HRV

This is an important article to keep in mind.  Just as in this latest article from Harvard, stimulation parameters really matter when trying to activate vagal activity.  This study is in animals and directly stimulation the vagus nerve.   If you get it wrong, you can get the opposite effect.  That is why I think my practice of monitoring HRV during treatment, and varying treatment (TAVNS, electroacupuncture etc…) is the safest approach.


Tsaava T, Datta-Chaudhuri T, Addorisio ME, et al. Specific vagus nerve stimulation parameters alter serum cytokine levels in the absence of inflammation. Bioelectron Med. 2020;6:8. Published 2020 Apr 10. doi:10.1186/s42234-020-00042-8



Electrical stimulation of peripheral nerves is a widely used technique to treat a variety of conditions including chronic pain, motor impairment, headaches, and epilepsy. Nerve stimulation to achieve efficacious symptomatic relief depends on the proper selection of electrical stimulation parameters to recruit the appropriate fibers within a nerve. Recently, electrical stimulation of the vagus nerve has shown promise for controlling inflammation and clinical trials have demonstrated efficacy for the treatment of inflammatory disorders. This application of vagus nerve stimulation activates the inflammatory reflex, reducing levels of inflammatory cytokines during inflammation.


Here, we wanted to test whether altering the parameters of electrical vagus nerve stimulation would change circulating cytokine levels of normal healthy animals in the absence of increased inflammation. To examine this, we systematically tested a set of electrical stimulation parameters and measured serum cytokine levels in healthy mice.


Surprisingly, we found that specific combinations of pulse width, pulse amplitude, and frequency produced significant increases of the pro-inflammatory cytokine tumor necrosis factor (TNF), while other parameters selectively lowered serum TNF levels, as compared to sham-stimulated mice. In addition, serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) were significantly increased by select parameters of electrical stimulation but remained unchanged with others.


These results indicate that electrical stimulation parameter selection is critically important for the modulation of cytokines via the cervical vagus nerve and that specific cytokines can be increased by electrical stimulation in the absence of inflammation. As the next generation of bioelectronic therapies and devices are developed to capitalize on the neural regulation of inflammation, the selection of nerve stimulation parameters will be a critically important variable for achieving cytokine-specific changes.

Keywords: Inflammatory reflex, Neuromodulation, Tumor necrosis factor, Interleukin-10