To achieve selective activation of the efferent pathways while blocking the afferent pathways, the researchers combined cVN stimulation with kilohertz electrical stimulation (KES), which their previous research found to provide a “virtual vagotomy” in blocking nerve activity in the cVNS.5 The results of the present study show that pairing the techniques increased the anti-inflammatory effects of cVN stimulation.

“Our results suggest a way to optimize clinical work on vagus nerve stimulation for reducing systemic inflammation,” said Yogi A. Patel, from the department of bioengineering at the Georgia Institute of Technology in Atlanta. “Most importantly, they suggest that stimulating both the efferent and afferent pathways may lead to mixed activation of proinflammatory and anti-inflammatory pathways, which may not be ideal for clinical applications,” he told Rheumatology Advisor.

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SetPoint also recently announced positive results in a trial of vagus nerve stimulation in patients with Crohn’s disease, and similar devices made by other companies have demonstrated promising results in treating conditions such as hypertension and heart failure.6

Additional, larger trials will be needed before SetPoint’s device for RA could be released to market, and it is also unclear when the use of KES might be available. This would “require additional work and evaluation to determine safety and efficacy in studies lasting weeks to months,” said Mr Patel. “This makes it difficult to state an anticipated timeline to market.”

These recent findings can help guide future investigations in the use of “bioelectronic medicine” in diseases that are currently treated with medications.

Summary and Clinical Applicability

Vagus nerve stimulation has shown promise in animal and human studies in reducing inflammation and disease severity in rheumatoid arthritis. 

Limitations and Disclosures

  • Additional human trials and larger studies are needed.

Several authors of the SetPoint study are employed by the company.

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  1.  Levine YA, Koopman FA, Faltys M, et al. Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. PLoS One. 2014;9(8):e104530.

  2. Koopman FA, Chavan SS, Miliko S, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proceed Natl Acad Sci. 2016;113(29):8284-8289.

  3. Long term extension study for SPM-005 participants. Accessed January 19, 2017.

  4. Patel YA, Saxena T, Bellamkonda RV, Butera RJ. Kilohertz frequency nerve block enhances anti-inflammatory effects of vagus nerve stimulation. Sci Rep. 2017;7:39810. 

  5. Patel YA, Butera RJ. Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation. J Neurophysiol. 2015;113(10):3923-3929. 

  6. Med Device Online. Electronic Implant Could Ease Hypertension; Nerve Stimulation in Neck May Reduce Heart Failure Symptoms. and  Accessed January 19, 2017.

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