Effects of transcutaneous auricular vagus nerve stimulation on motor and gait performance in Parkinson's disease: a meta-analysis of randomized controlled trials.

Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological treatment that works by delivering electrical currents via electrodes attached to the skin at the site of pain. It can be an alternative to pharmacological treatments. The mechanism of action of TENS for pain relief is related to the inhibition of the transmission of painful stimuli, release of endogenous opioids, and reduced muscle ischaemia of the uterus. Although it has been used for primary dysmenorrhoea ((PD); period pain or menstrual cramps), evidence of the efficacy and safety of high-frequency TENS, low-frequency TENS, or other treatments for PD is limited. To evaluate the effectiveness and safety of transcutaneous electrical nerve stimulation (TENS) in comparison with placebo, no treatment, and other treatments for primary dysmenorrhoea (PD). We searched the Gynaecology and Fertility Group's Specialized Register of controlled trials, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, CINAHL, and the Korean and Chinese language databases up to 9 April 2024. We also searched for ongoing trials in trials registries and the reference lists of relevant studies for additional trials. Language restrictions were not applied. We included randomized controlled trials (RCTs) that included women (aged 12 to 49 years) with PD. Included trials compared low-frequency TENS or high-frequency TENS with other TENS, placebo, or other treatment. Four review authors screened the trials, extracted the data according to the protocol, assessed the risk of bias using RoB 2, and assessed the certainty of evidence for all review comparisons and primary outcomes (i.e. pain relief and adverse effects) using the GRADE approach. This review replaces the current review, published in 2009. We included 20 RCTs involving 585 randomized women with high-frequency TENS, low-frequency TENS, placebo or no treatment, or other treatment. We included five comparisons: high-frequency TENS versus placebo or no treatment, low-frequency TENS versus placebo or no treatment, high-frequency TENS versus low-frequency TENS, high-frequency TENS versus other treatments, and low-frequency TENS versus other treatments. High-frequency TENS versus placebo or no treatment High-frequency TENS may reduce pain compared with placebo or no treatment (mean difference (MD) -1.39, 95% confidence interval (CI) -2.51 to -0.28; 10 RCTs, 345 women; low-certainty evidence; I2 = 88%). Two out of three RCTs reported no adverse effects and hence we were unable to estimate the effect of high-frequency TENS on adverse effects. Low-frequency TENS versus placebo or no treatment Low-frequency TENS may reduce pain compared with placebo or no treatment (MD -2.04, 95% CI -2.95 to -1.14; 3 RCTs, 645 women; low-certainty evidence; I2 = 0%). No trials reported adverse effects for this comparison. High-frequency TENS versus low-frequency TENS It is uncertain whether high-frequency TENS had an effect on pain relief compared with low-frequency TENS (MD 0.89, 95% CI -0.19 to 1.96; 3 RCTs, 54 women; low-certainty evidence; I2 = 0%). One trial contributed data on adverse effects but no adverse events occurred. High-frequency TENS versus other treatments It is uncertain whether high-frequency TENS had an effect on pain relief compared to acupressure (MD -0.66, 95% CI -1.72 to 0.40; 1 RCT, 18 women; very low-certainty evidence), acetaminophen (paracetamol) (MD -0.98, 95% CI -3.30 to 1.34; 1 RCT, 20 women; very low-certainty evidence), and interferential current therapy (MD -0.03, 95% CI -1.04 to 0.98; 2 RCTs, 62 women; low-certainty evidence; I2 = 0%). The occurrence of adverse effects may not differ significantly between high-frequency TENS and NSAIDs (OR 12.06, 95% CI 0.26 to 570.62; 2 RCTs, 88 women; low-certainty evidence; I2 = 78%). Low-frequency TENS versus other treatments It is uncertain whether low-frequency TENS had an effect on pain relief compared with acetaminophen (MD -1.48, 95% CI -3.61 to 0.65; 1 RCT, 20 women; very low-certainty evidence). No trials reported adverse effects for this comparison. High-frequency TENS and low-frequency TENS may reduce pain compared with placebo or no treatment. We downgraded the certainty of the evidence because of the risk of bias. Future RCTs should focus more on secondary outcomes of this review (e.g. requirement for additional analgesics, limitation of daily activities, or health-related quality of life) and should be designed to ensure a low risk of bias.

To investigate the combined effect of transcranial magnetic stimulation (TMS) and transcranial direct current stimulation on improving lower limb function in stroke patients. Randomized controlled trial. Subacute stroke patients. 169 post-stroke hemiplegia patients were randomly divided into 4 groups (control, transcranial direct current stimulation, transcutaneous auricular vagus nerve stimulation, and transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation) and evaluated using the Fugl-Meyer Assessment-Lower Extremity (FMA-LL), Timed Up-and-Go (TUG) test, Modified Barthel Index (MBI), Berg Balance Scale (BBS), gait parameters, and surface electromyography (sEMG). Significant improvements in FMA-LL, MBI, BBS, TUG, gait parameters, and sEMG were noted in the intervention groups compared with the control, with the transcutaneous auricular vagus nerve stimulation combined with transcranial direct current stimulation group showing the most pronounced improvements. Differences in some outcomes were also notable between the transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation groups. The combination of transcutaneous auricular vagus nerve stimulation and transcranial direct current stimulation effectively enhances gait, balance, and daily living activities in subacute stroke patients. These benefits are likely due to transcutaneous auricular vagus nerve stimulation activating the solitary and trigeminal nuclei and transcranial direct current stimulation stimulating the motor cortex. Wearable gait analysis systems and electromyography are valuable in clinical gait assessment for these patients.

The inclusion of two new trials in this update did not change the main conclusions of the original review. The current evidence is very uncertain about the effect of chest physiotherapy on improving mortality and cure rate in adults with pneumonia. Some physiotherapies may slightly shorten hospital stays, fever duration, and ICU stays, as well as mechanical ventilation. However, all of these findings are based on very low certainty evidence and need to be further validated.

Transcutaneous auricular vagus nerve stimulation for managing pain: A scoping review

Pharmacological interventions for pruritus in adult palliative care patients.

Folic acid supplementation and malaria susceptibility and severity among people taking antifolate antimalarial drugs in endemic areas.

Among the noninvasive electrical stimulation methods, transcutaneous auricular vagus nerve stimulation (taVNS) regulates the activity of various neural networks in the brain and autonomic nervous system and is expected to be applied clinically in many areas, including in patients with central nervous system, psychiatric, and cardiac diseases. Although systematic reviews and meta-analyses have been conducted on safety and efficacy, the variability of stimulation parameters and the lack of consistency in their effects remain significant issues. Therefore, the present study aimed to provide a comprehensive view of the safety, parameters, and efficacy of taVNS by focusing on studies in healthy participants, patients with stroke, and patients with Parkinson’s disease. A literature search was conducted from October 14 to 25 November 2024, using PubMed, Google Scholar, Web of Science, the Cochrane Library, and Scopus. The following search terms were used: “noninvasive VNS or nVNS or noninvasive vagus nerve stimulation,” “transcutaneous vagus nerve stimulation or tVNS,” and “transcutaneous auricular vagus nerve stimulation or taVNS.” In total, 154 papers were included, of which 139 were on healthy participants, nine on patients with stroke, and six on patients with Parkinson’s disease. The safety of taVNS was relatively high. Although minor side effects were reported, no serious adverse events were attributed to taVNS parameters used. taVNS could regulate brain activity, motor and mental functions, and autonomic nervous system activity in patients with stroke and Parkinson’s disease. Modulation of the autonomic nervous system and cortical excitability was also observed in healthy individuals. However, these effects may depend on the stimulation parameters. The lack of reports on safety and the stimulation parameters used was also highlighted. Further validation of parameters and accumulation of evidence regarding the efficacy of taVNS are necessary.

This systematic review aimed to evaluate the effect of transcutaneous auricular vagus nerve stimulation on heart rate variability and baroreflex sensitivity in healthy populations. PubMed, Scopus, the Cochrane Library, Embase, and Web of Science were systematically searched for controlled trials that examined the effects of transcutaneous auricular vagus nerve stimulation on heart rate variability parameters and baroreflex sensitivity in apparently healthy individuals. Two independent researchers screened the search results, extracted the data, and evaluated the quality of the included studies. From 2458 screened studies, 21 were included. Compared with baseline measures or the comparison group, significant changes in the standard deviation of NN intervals, the root mean square of successive RR intervals, the proportion of consecutive RR intervals that differ by more than 50ms, high-frequency power, low-frequency to high-frequency ratio, and low-frequency power were found in 86%, 75%, 69%, 47%, 36%, and 25% of the studies evaluating the effects of transcutaneous auricular vagus nerve stimulation on these indices, respectively. Baroreflex sensitivity was evaluated in six studies, of which a significant change was detected in only one. Some studies have shown that the worse the basic autonomic function, the better the response to transcutaneous auricular vagus nerve stimulation. The results were mixed, which may be mainly attributable to the heterogeneity of the study designs and stimulation delivery dosages. Thus, future studies with comparable designs are required to determine the optimal stimulation parameters and clarify the significance of autonomic indices as a reliable marker of neuromodulation responsiveness.

This review is based on four trials (1731 women) with an overall unclear risk of bias. The trials provided data on most primary outcomes and suggest that tighter glycaemic control may increase the risk of hypertensive disorders of pregnancy. The risk of birth of a large-for-gestational-age infant and perinatal mortality may be similar between groups, and tighter glycaemic targets may result in a possible reduction in composite of death or severe infant morbidity. However, the CIs for these outcomes are wide, suggesting both benefit and harm. There remains limited evidence regarding the benefit of different glycaemic targets for women with GDM to minimise adverse effects on maternal and infant health. Glycaemic target recommendations from international professional organisations vary widely and are currently reliant on consensus given the lack of high-certainty evidence. Further high-quality trials are needed, and these should assess both short- and long-term health outcomes for women and their babies; include women's experiences; and assess health services costs in order to confirm the current findings. Two trials are ongoing.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that activates vagal afferents projecting to prefrontal-limbic circuits implicated in attention, memory, and emotion regulation. Preliminary studies suggest that taVNS may enhance cognitive performance; however, the evidence remains fragmented across domains and populations. This systematic review and meta-analysis aim to (1) quantify the overall effects of taVNS on cognitive functions, (2) examine its efficacy across clinical and non-clinical populations, and (3) identify moderators influencing variability in outcomes, including stimulation parameters, participant characteristics, and study design features. Following PRISMA-P guidelines, this protocol will be prospectively registered with PROSPERO. Six databases (PubMed, EMBASE, PsycINFO, Web of Science, CENTRAL, and Scopus) and major trial registries will be systematically searched. Eligible studies include randomised controlled trials assessing validated cognitive outcomes following taVNS compared with sham or active controls. Effect sizes will be calculated as Hedges' g and pooled using random-effects models. Heterogeneity will be evaluated with I² and τ statistics; moderator and meta-regression analyses will explore dose-response and population effects. Risk of bias will be assessed with RoB 2 for randomised trials and ROBINS-I for non-randomised studies, and the certainty of evidence will be rated using GRADE separately by study design. This review will provide the first quantitative meta-analytic synthesis of taVNS-induced cognitive modulation across executive, attentional, affective, and learning domains in both clinical and healthy populations, complementing recent narrative syntheses by offering pooled effect size estimates, formal heterogeneity assessment, and a GRADE-rated evidence hierarchy. By delineating domain-specific efficacy and optimal stimulation parameters, the findings aim to inform future clinical applications and the development of standardized neuromodulation protocols.

BackgroundTranscutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects.Methods/designThe study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p < 0.05.DiscussionThis study will provide evidence concerning the combined effects of TENS and TaVNS on pain threshold in pain-free participants. Based on the outcomes, a greater understanding of how TENS and TaVNS, when used in conjunction, can modulate pain pathways.Trial registrationClinicalTrials.gov NCT06361381. Registered on 09 April 2024.

Background &amp; objective: Low back pain is a common problem, especially in the young and middle-aged working people, and is often very resistant to the conventional management. We evaluated the impact of transcutaneous auricular vagus nerve stimulation (tVNS), applied in conjunction with an exercise treatment program, on disability in chronic low back pain patients.&#x0D; Methodology: The study was conducted from June to October 2022. Twenty-two patients aged 42.18 ± 9.91 y, with Numerical Pain Rating Scale (NPRS) score 5.64 ± 1.09 and Roland Morris Disability Questionnaire (RMDQ) score 10 ± 4.670, were randomly assigned to two groups. The control group received only exercise therapy (EXC group, n = 11), and the intervention group received exercise and tVNS therapy (EXC + tVNS group, n = 11). The primary outcome was RMDQ, measured before and after the intervention.&#x0D; Result: The mean RMDQ was significantly improved in both groups. In the intervention group the improvement was from 9.45 ± 4.44 to 2.18 ± 2.71 (P = 0.000), in the control group it was from 10.55 ± 5.05 to 2.36 ± 2.06 (P = 0.001). Inter-group comparison showed no significant difference. The effect size of the control group (2.12) was similar with the intervention group (1.98).&#x0D; Conclusion: Addition of 2-weeks tVNS to exercise therapy did not show superior effect on disability improvement compared to exercise only in chronic low back pain. Exercise alone was sufficient to improve the mean RMDQ.&#x0D; Abbreviations: CLBP: Chronic low back pain; EXC: Exercise; tVNS: Transcutaneous auricular vagus nerve stimulation; NPRS: Numerical pain rating scale; RMDQ: Roland Morris disability questionnaire&#x0D; Key words: Chronic low back pain; Disability; Exercise; Transcutaneous Auricular Vagus Nerve Stimulation&#x0D; Citation: Uzlifatin Y, Arfianti L, Wardhani IL, Hidayati HB, Melaniani S. Effect of transcutaneous auricular vagus nerve stimulation in addition to exercise on disability in chronic low back pain patients: a randomized controlled study. Anaesth. pain intensive care 2022;27(1):73−81; DOI: 10.35975/apic.v27i1.2084&#x0D; Received: December 07, 2022; Reviewed: December 28, 2022; Accepted: January 11, 2022

This study aimed to investigate the effects of adding transcutaneous auricular vagus nerve stimulation (taVNS) to robotic rehabilitation on functional outcomes and neuromuscular activity in patients with ischemic stroke. This randomized controlled clinical trial employed a pre–post study design and was conducted in a hospital-based physiotherapy and rehabilitation clinic. A total of 40 patients with ischemic stroke, aged 18–65 years, were randomly assigned to either a robotic rehabilitation group (RRG) or a combined vagus nerve stimulation and robotic rehabilitation group (VRRG). Spasticity, walking speed, motor function, quality of life, muscle activity, and pain were assessed at baseline and after six weeks of treatment. Primary outcome measures were walking speed, motor function assessed by the Fugl–Meyer Assessment, and pain intensity. Secondary outcomes included electrophysiological measurements (H-reflex and F-wave parameters) and quality of life. Within-group analyses showed significant improvements in all outcomes in the VRRG (p < 0.05), whereas all outcomes except pain improved significantly in the RRG (p < 0.05). Between-group comparisons demonstrated greater improvements in walking speed in the VRRG compared with the RRG (mean difference − 1.84 s, 95% CI − 3.7 to − 0.7; r = 0.43; p = 0.006) and greater pain reduction in the VRRG (mean difference − 1.55, 95% CI − 2.5 to − 0.1; r = 0.30; p = 0.048). In contrast, a greater reduction in the Hmax/Mmax amplitude ratio—an electrophysiological marker of spinal excitability—was observed in the RRG. The findings suggest that transcutaneous auricular vagus nerve stimulation combined with robotic rehabilitation may provide additional benefits in terms of walking speed and pain reduction in patients with ischemic stroke. The study was registered at ClinicalTrials.gov on April 19, 2024. (Identifier: NCT06381089).

We found that acupuncture may not play a more clinically meaningful role than sham in relieving pain immediately after treatment or in improving quality of life in the short term, and acupuncture possibly did not improve back function compared to sham in the immediate term. However, acupuncture was more effective than no treatment in improving pain and function in the immediate term. Trials with usual care as the control showed acupuncture may not reduce pain clinically, but the therapy may improve function immediately after sessions as well as physical but not mental quality of life in the short term. The evidence was downgraded to moderate to very low-certainty considering most of studies had high risk of bias, inconsistency, and small sample size introducing imprecision. The decision to use acupuncture to treat chronic low back pain might depend on the availability, cost and patient's preferences.

NSAIDs may be better than placebo and are probably better than opioids at relieving pain from uterine cramping/involution following vaginal birth. NSAIDs and paracetamol may be as effective as each other, whereas opioids may be more effective than placebo. Due to low-certainty evidence, we are uncertain about the effectiveness of other forms of pain relief. Future trials should recruit adequate numbers of women and ensure greater generalisability by including breastfeeding women. In addition, further research is required, including a survey of postpartum women to describe appropriately their experience of uterine cramping and involution. We identified nine ongoing studies, which may help to increase the level of certainty of the evidence around pain relief due to uterine cramping in future updates of this review.