Author: Paulo S de Melo1, Anna C Gianlorenco2, Anna Marduy3, Chi K Kim4, Hyuk Choi5, Jae-Jun Song6, Felipe Fregni7
Affiliation: <sup>1</sup> Medicine, Escola Bahiana de Medicina e Saúde Pública, Salvador, Bahia, Brazil; Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
<sup>2</sup> Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Therapy, Federal University of São Carlos, Brazil.
<sup>3</sup> Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Medicine, União Metropolitana de Ensino e Cultura (UNIME), Salvador, Bahia, Brazil.
<sup>4</sup> Department of Neurology, Korea University Guro Hospital, Seoul, South Korea.
<sup>5</sup> Department of Medical Sciences, Graduate School of Medicine, Korea University, Seoul, South Korea; Neurive Co, Ltd, Gimhae, South Korea.
<sup>6</sup> Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Medical Center, Seoul, South Korea; Neurive Co, Ltd, Gimhae, South Korea.
<sup>7</sup> Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: Fregni.Felipe@mgh.harvard.edu.
Conference/Journal: Neuromodulation
Date published: 2024 May 25
Other:
Pages: S1094-7159(24)00065-5 , Special Notes: doi: 10.1016/j.neurom.2024.03.002. , Word Count: 315
Objective:
We aimed to conduct a systematic review and meta-analysis assessing the antiinflammatory effects of various VNS methods while exploring multiple antiinflammatory pathways.
Materials and methods:
We included clinical trials that used electrical stimulation of the vagus nerve and assessed inflammatory markers up to October 2022. We excluded studies lacking control groups, those with combined interventions, or abstracts without full text. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews. For each inflammatory marker, a random-effects meta-analysis using the inverse variance method was performed. Methods used include transcutaneous auricular VNS (taVNS), transcutaneous cervical VNS (tcVNS), invasive cervical VNS (iVNS), and electroacupuncture VNS (eaVNS). Main reported outcomes included tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, C-reactive protein (CRP), and IL-10. Risk of bias was evaluated using the Cochrane Collaboration Tool (RoB 2.0).
Results:
This review included 15 studies, involving 597 patients. No statistically significant general VNS effect was observed on TNF-α, IL-6, and IL-1ß. However, CRP, IL-10, and interferon (IFN)-γ were significantly modulated by VNS across all methods. Subgroup analysis revealed specific stimulation techniques producing significant results, such as taVNS effects in IL-1ß and IL-10, and iVNS in IL-6, whereas tcVNS and eaVNS did not convey significant pooled results individually. Cumulative exposure to VNS, higher risk of bias, study design, and pulse width were identified as effect size predictors in our meta-regression models.
Conclusions:
Pooling all VNS techniques indicated the ability of VNS to modulate inflammatory markers such as CRP, IL-10, and IFN-γ. Individually, methods such as taVNS were effective in modulating IL-1ß and IL-10, whereas iVNS modulated IL-6. However, different VNS techniques should be separately analyzed in larger, homogeneous, and powerful studies to achieve a clearer and more consistent understanding of the effect of each VNS method on the inflammatory system.
Keywords: Inflammatory biomarkers; meta-analysis; meta-regression; systematic review; vagus nerve stimulation.
PMID: 38795094 DOI: 10.1016/j.neurom.2024.03.002