The main symptom of peripheral arterial disease (PAD) is intermittent claudication (IC),¹ which results from an insufficient oxygen supply to skeletal muscles during activity.² IC is characterized by discomfort in the lower limbs during physical exertion due to muscle ischemia, which subsides with rest.^2-6 It is associated with gait alterations, reduced functional capacity,⁷ and a decline in quality of life among individuals with PAD.⁸

Regular exercise, whether performed in supervised programs or at home, is recommended and has shown positive outcomes in enhancing functional capacity in people with PAD.⁶ Clinical trials and meta-analyses^3-6,9 have demonstrated that supervised exercise programs effectively improve IC symptoms and increase walking distance. Among the many benefits of exercise, the most notable are improved muscle adaptation, enhanced oxidative capacity, reduced reliance on anaerobic glycolysis, and decreased lactate accumulation.¹⁰

The most current physical exercise recommendation for the treatment of IC is walking at an intensity close to the point of symptom limitation, performed three times per week for at least thirty minutes. A duration of eight weeks is sufficient to observe improvements in the functional capacity of these individuals.¹⁰ While walking is the most recommended and effective modality for reducing claudication symptoms, other forms of exercise, such as modified aerobic training,¹¹ resistance training,¹² and warm-water exercise therapy,¹³ have also been employed and have shown positive results in individuals with PAD.

Although the benefits of exercise therapy are well established, many individuals with IC remain inactive and show low adherence to supervised training programs.¹⁴ In one study, after a three-month follow-up, only 16% of patients with IC continued participating in an unsupervised walking program.¹⁵ One of the main reasons for this low adherence is the requirement to walk at an intensity close to moderate or maximum claudication symptoms.¹⁶ Given the challenge of implementing a treatment that induces discomfort in individuals with PAD, noninvasive electrostimulation has emerged as a safe and low-cost alternative for improving physical performance in this population (Central Illustration).¹⁴

Noninvasive electrostimulation therapies are typically delivered through transcutaneous nerve stimulation, in which electric currents are applied via electrodes placed on the skin. The resulting stimulus directly affects peripheral mechanoceptors.¹⁷ Studies in experimental models^18,19 have shown that low-frequency noninvasive electrostimulation promotes increased circulatory activation, enhances mitochondrial enzymatic activity, and improves the oxidative capacity of type I muscle fibers.²⁰

The technique may also contribute to the acute delay of claudication, as it is associated with the inhibition of muscle sympathetic activity. The effects produced by electrostimulation are similar to those of endogenous opioids²¹ and are closely linked to increased capillary density, enhanced resistance to fatigue, and improved oxygen uptake in ischemic muscles.^20,22-24

Given the strong external validity of this therapy as an adjunctive approach to reducing intermittent claudication in individuals with PAD, the aim of the present study was to evaluate, through a systematic review, the effects of noninvasive electrostimulation on walking distance and claudication-related pain in individuals with lower limb PAD.

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology.²⁵

The search strategy identified 25 studies (Figure 1). After applying the predefined inclusion criteria, seven studies were selected, comprising a total of 314 participants with a mean age of 66.8 ± 3.6 years. All participants presented with intermittent claudication (Fontaine stage II), which was the focus of this review. Although inclusion criteria varied across studies, the presence of an ankle-brachial index (ABI) < 0.90, stable IC, and limited walking capacity (Fontaine stage II) was a consistent requirement.

A summary of the studies and their main findings regarding the use of noninvasive electrostimulation for the treatment of IC is presented in Table 1. Analysis of the data reveals that most studies reported a positive effect of noninvasive electrostimulation on walking performance, particularly in terms of increased pain-free and maximum walking distances. Low-frequency transcutaneous electrical nerve stimulation (TENS) and neuromuscular electrical stimulation (NMES) were the modalities most consistently associated with functional improvement. Studies with longer intervention durations or stimulation applied to multiple muscle groups tended to show more pronounced effects. Notably, few studies reported adverse events, indicating that these modalities are generally safe and well tolerated. Collectively, these findings support the potential clinical utility of noninvasive electrostimulation, particularly for patients with limited access to or tolerance for traditional exercise therapy.

The results of this review indicate that noninvasive electrostimulation applied to the skeletal muscles of individuals with PAD can help reduce pain associated with intermittent claudication and improve functional capacity. These findings align with existing literature, such as the systematic review by Jéhannin et al.,³² which also examined the use of electrical stimulation in patients with PAD. However, our analysis differs by employing more stringent inclusion criteria, focusing exclusively on randomized controlled trials involving therapeutic interventions, and encompassing a range of noninvasive electrostimulation modalities. This approach enabled a more robust evaluation of the effects on pain and functional capacity, particularly in the context of intermittent claudication.

Most studies applied noninvasive electrostimulation to the plantar flexor muscles,^27-31 and low-frequency stimulation – regardless of the application site – proved to be an effective option for increasing the distance walked until the onset of maximum claudication. Both acute stimulation using TENS and chronic stimulation demonstrated significant improvements in pain-free walking distance.^27,29

Four types of noninvasive electrostimulation were identified: NMES,^22,27 TENS,^29,30 functional electrical stimulation (FES),^28,31 and electroacupuncture.³³ Each modality operates with distinct electrical parameters and is believed to enhance walking ability by acting through vascular and/or non-vascular mechanisms. Proposed hypotheses for symptom improvement and pain relief in individuals with PAD include increased capillary density, transformation of muscle fibers to more oxidative types, analgesic effects, and reduced peripheral sympathetic activity.^29,34

Seenan et al.³⁰ demonstrated that low-frequency TENS applied to the gastrocnemius muscle significantly increased both initial and absolute claudication distances compared to placebo. These results suggest that even acute sessions of noninvasive electrostimulation may temporarily enhance peripheral perfusion or reduce pain perception, potentially via activation of endogenous opioid pathways. These findings support the proposed analgesic mechanisms of TENS and highlight its potential role as a pre-exercise or rehabilitation support strategy. However, the lack of long-term follow-up limits conclusions regarding its sustained clinical benefits.

In contrast, using a similar protocol, Labrunée et al.²⁹ observed that TENS applied at 10 Hz to the gastrocnemius and quadriceps regions significantly delayed the onset of pain compared to placebo. This finding supports the hypothesis that low-frequency stimulation may preferentially modulate afferent nociceptive input and enhance ischemic muscle metabolism. The inclusion of the quadriceps as an additional stimulation site may have contributed to greater muscle recruitment, thereby improving walking tolerance. These results provide a rationale for exploring multi-site stimulation protocols in future clinical trials.^24,35

The study by Anderson et al.²⁷ offered valuable insights by demonstrating that short sessions of electrical muscle stimulation (EMS) can increase arterial blood flow in symptomatic limbs without inducing ischemia or muscle discomfort. This supports the vascular mechanism of benefit associated with electrostimulation and suggests its potential use in early rehabilitation stages or in patients who are intolerant to exercise. However, the absence of claudication distance measurements and the short duration of the intervention limit the generalizability of these findings.

Another type of noninvasive electrostimulation identified was auricular nerve stimulation via electroacupuncture.³³ Although not widely used, it has shown promise as a conservative therapeutic alternative for improving the quality of life in individuals with PAD at Fontaine stage II, demonstrating benefits in walking speed and stair-climbing ability. In another study that applied this technique during the postoperative period following revascularization surgery, electroacupuncture also played a significant role in reducing postoperative pain and vascular reactivity.³⁶

Although noninvasive electrostimulation is generally considered safe and easy to administer, its application must account for the absence of specific contraindications. These include the presence of peripheral neuropathy – particularly reduced sensitivity in areas where electrodes are placed – pregnancy, cardiac pacemakers, epilepsy, and known allergies to electrode materials.³⁷

Finally, in studies involving noninvasive electrostimulation for PAD, there remains a shortage of research conducted in human models. It is important to note that each type of noninvasive electrostimulation may produce distinct effects through vascular and/or non-vascular mechanisms, depending on the type of stimulus and programming parameters used. Other forms of electrostimulation were identified but excluded from this review because they addressed outcomes outside its scope – specifically, studies involving patients at Fontaine stages III and IV or those using invasive spinal electrostimulation.

Although the included studies involved participants with clinically well-defined PAD and employed standardized diagnostic criteria, the small sample sizes and limited diversity in demographic and clinical profiles restrict the external validity of this review. Caution is warranted when generalizing these findings, particularly to populations with comorbidities not addressed in the original studies, such as diabetes, obesity, or coronary artery disease. Further large-scale trials with broader inclusion criteria are needed to enhance the generalizability and clinical applicability of the results.

The results of this review indicate that noninvasive electrostimulation of the lower limbs may help reduce claudication-related pain when used alongside conventional therapeutic measures for treating IC, such as supervised exercise, pharmacological interventions, and lifestyle modifications. Additionally, its effects may contribute to increased walking distance in this patient population, positioning it as a low-cost adjuvant therapeutic option for individuals with symptomatic PAD.

However, further randomized clinical trials with lower risk of bias are needed to determine the most effective modality, as variations in stimulation parameters—such as frequency, wavelength, and application site – can lead to differing outcomes. Moreover, the selection of noninvasive electrostimulation therapy should be tailored to the individual needs of each patient.