Transcutaneous vagus nerve stimulation effects on chronic pain: systematic review and meta-analysis
Valton Costa,
Anna Carolyna Gianlorenço,
Maria Fernanda Andrade,
Lucas Camargo,
Maryela Menacho,
Mariana Arias Avila,
Kevin Pacheco-Barrios,
Hyuk Choi,
Jae-Jun Song,
Felipe Fregni
Affiliations
Valton Costa
a Neurosciences Laboratory, Physical Therapy Department, Federal University of Sao Carlos, Sao Carlos, SP, Brazil
Anna Carolyna Gianlorenço
a Neurosciences Laboratory, Physical Therapy Department, Federal University of Sao Carlos, Sao Carlos, SP, Brazil
Maria Fernanda Andrade
b Spaulding Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Lucas Camargo
b Spaulding Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Maryela Menacho
a Neurosciences Laboratory, Physical Therapy Department, Federal University of Sao Carlos, Sao Carlos, SP, Brazil
Mariana Arias Avila
c Study Group on Chronic Pain (NEDoC), Laboratory of Research on Electrophysical Agents (LAREF), Physical Therapy Department, Federal University of Sao Carlos, Sao Carlos, SP, Brazil
Kevin Pacheco-Barrios
b Spaulding Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Hyuk Choi
e Department of Medical Sciences, Graduate School of Medicine, Korea University, Seoul, South Korea
Jae-Jun Song
f Neurive Co, Ltd, Gimhae, South Korea
Felipe Fregni
b Spaulding Neuromodulation Center and Center for Clinical Research Learning, Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Abstract. Chronic pain is one of the major causes of disability with a tremendous impact on an individual's quality of life and on public health. Transcutaneous vagus nerve stimulation (tVNS) is a safe therapeutic for this condition. We aimed to evaluate its effects in adults with chronic pain. A comprehensive search was performed, including randomized controlled trials published until October 2023, which assessed the effects of noninvasive tVNS. Cohen's d effect size and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were performed. Fifteen studies were included. The results revealed a mean effect size of 0.41 (95% CI 0.17-0.66) in favor of tVNS as compared with control, although a significant heterogeneity was observed (χ2 = 21.7, df = 10, P = 0.02, I2 = 53.9%). However, when compared with nonactive controls, tVNS shows a larger effect size (0.79, 95% CI 0.25-1.33), although the number of studies was small (n = 3). When analyzed separately, auricular tVNS and cervical tVNS against control, it shows a significant small to moderate effect size, similar to that of the main analysis, respectively, 0.42 (95% CI 0.08-0.76, 8 studies) and 0.36 (95% CI 0.01-0.70, 3 studies). No differences were observed in the number of migraine days for the trials on migraine. This meta-analysis indicates that tVNS shows promise as an effective intervention for managing pain intensity in chronic pain conditions. We discuss the design of future trials to confirm these preliminary results, including sample size and parameters of stimulation.
