Background: Vagus nerve stimulation (VNS) changes the function of cranial nerves by placing a small device in the body that sends electrical signals via the vagus nerve to the neck and brain stem. These signals alter pain responses from the brain, in turn helping with migraine management.

Objective: This paper looked at whether vagus nerve stimulation is an effective treatment for migraines.

Methods: Articles were searched via PubMed with the key terms “vagus nerve stimulation,” “migraine,” and “pain relief.” All studies included were original research articles, had human participants, and were published in English. Studies were excluded if they were review articles, involved non-human subjects, or were published in any language other than English.

Results: VNS is an effective treatment for migraines. It reduces attack frequency, pain intensity, and medication dependency.

Conclusion: To treat migraines, VNS can be used as an alternative to medications. It helps reduce the risk of medication overuse headaches (MOH), as well as other medication side effects such as compulsive medication use, and behavioral problems.

Migraines are ranked as the third most common neurological condition in the world [1]. This disorder is highly prevalent, and remains among the top three from ages 5 to 80 [1]. It is common among people of all ages, genders, and races, making it a universal burden [1]. Fifty percent of migraine patients self-treat their headaches, often leading to heavy reliance on medications such as analgesics and anti-emetics [1]. While taking medications as treatment is not inherently wrong, there are many health risks associated with it [1]. Medication overuse has been known to cause addiction, compulsive medication use, and behavioral problems [3]. It can also lead to medication-overuse headache (MOH), which is a common neurological disorder [3]. MOH often turns episodic headaches into chronic headache disorders, leading to severe suffering and disability [3]. Both migraines and MOH have critical effects on quality of life [1]. Recurrent attacks disrupt family dynamics, social activities, and occupational performance [1]. Furthermore, people with migraine disorders have higher rates of depression and anxiety compared to those without the condition [1]. Given these widespread personal, social, and clinical consequences, there is a growing need for effective non-pharmacological treatment options. In light of new treatments, vagus nerve stimulation (VNS) is currently being explored as a tool for migraine symptom relief [2]. During VNS, electrical signals are sent via the vagus nerve, which carries those messages up to the brain [2]. Consequently, a network of vagus nerve pathways is activated, connecting the brainstem with various brain regions [2]. In response to signals from the vagus nerve, brain regions implicated in migraines are brought to a more parasympathetic state, reducing pain [2]. VNS is an important alternative to medication use, as it mitigates the health risks of standard medicines and ensures a safer treatment for patients [2,3]. This review paper aims to evaluate the effects of VNS on migraines, either as a standalone intervention or in comparison with a sham treatment.

A literature search was conducted in PubMed to identify clinical studies exploring VNS as a migraine treatment. The search strategy combined the following keywords: “vagus nerve stimulation,” “migraine,” and “pain relief.” All studies included were original research articles, had human participants, and were published in English. Studies were excluded if they were review articles, involved non-human subjects, or were published in any language other than English.

Each of the studies shown in Table 1 published similar results regarding the effectiveness of vagus nerve stimulation in migraine pain relief, reduced headache days, decreased need for rescue medications, and altered connectivity of brain regions [4-8]. Study one looked at how transcutaneous auricular vagus nerve stimulation (taVNS) compares to a sham treatment [4]. The group of taVNS patients had significantly fewer migraine attack days than the sham group, and during these days, their pain intensity was noticeably lower [4]. Furthermore, taVNS increased connectivity between the anterior cingulate cortex, medial prefrontal cortex, and motor-related thalamus subregion [4]. It also decreased the connectivity between the postcentral gyrus, precuneus, and the occipital cortex-related thalamus subregion [4]. These connectivity changes altered sensory processing pathways, which led to pain relief in the taVNS patients [4]. Study two emphasized how the nucleus tractus solitarius, locus coeruleus, periaqueductal grey, raphe magnus, thalamus, and hypothalamus all activate a neural pathway, as shown in Figure 1 [5]. This pathway reduced pain and migraine frequency [5]. It also explored the results of nVNS treatment compared to a sham treatment [5]. The primary outcomes of this study were reduced migraine attack days and pain-free status within 30 min of nVNS use [5]. Two of the six trials in this study saw a decrease in migraine attack days in 4 weeks, and one trial saw a decrease in migraine attacks per week [5]. Secondary outcomes included the status of pain relief at 30 and 60 min, use of rescue medication, satisfaction, adverse events, and pain-free status in ≥50% of treated migraines [5]. The number of patients who reached pain-free status for at least 50% of treated headaches was much higher in the nVNS group compared to the sham group (OR: 2.15; 95% CI: 1.27–3.66; p=0.005) [5]. Study three found that following non-invasive vagus nerve stimulation (nVNS) treatment, 27 of 48 patients (56.3%) felt pain relief at 1 hour, and 17 of these patients (35.4%) were pain-free [6]. At 2 hours, 31 of 48 (64.6%) patients felt pain relief, and 19 of these patients (39.6%) were pain-free [6]. In study four, which compared the results of a nVNS device to those of a sham device, three main periods were looked at: the double-blind, observational, and open-label [7]. During the double-blind period of this study, at 60 minutes post-treatment, 16.3% of the nVNS group’s migraines were pain-free, and at 120 minutes, 22.9% of attacks were pain-free [7]. For the sham group, the pain-free results were 8.6% at 60 minutes and 14.8% at 120 minutes [7]. For all migraines, the nVNS group’s mean decrease in pain score at 60 minutes (0.42) was significantly larger than that of the sham group’s (0.22) [7]. During the observational period, pain-free and pain-relief results were ≥75% at 24 hours and ≥58% at 48 hours for both the nVNS and sham group [7]. During the open-label period, at 120 minutes 23.3% of all attacks were pain-free and 38.1% of them saw pain relief [7]. Altogether, the study found that the group of nVNS patients had a higher percent of pain-free status at 60 minutes (p=0.005) and at 120 minutes (p=0.0026) than the sham treatment group [7]. Lastly, study five observed a similar situation to studies two and four when comparing nVNS treatment to sham treatment [8]. After 30 minutes post-treatment, the percentage of nVNS patients who reported at least a 1-point decrease in pain score was 32.2%, whereas for the sham patients it was 18.5% [8]. At 60 minutes these percentages were 38.8% and 24.0%, and at 120 minutes they were 46.8% and 26.2% [8]. The percentage of nVNS patients that did not need rescue medications was 59.3% after the first attack, and 52.3% for all attacks [8]. For the sham group, these percentages were 41.9% after the first attack and 37.3% for all attacks [8]. Overall, each of these studies consistently revealed that vagus nerve stimulation was effective in relieving migraine pain, lowering the number of headache days, reducing the use of rescue medications, and modifying brain connectivity [4-8].

Table 1. Summary of Results

Figure 1. Diagram of various brain regions affected by VNS.

Each of the five studies found that vagus nerve stimulation (VNS) is an effective treatment for migraine pain and reduces the frequency of attacks [4-8]. Specifically, VNS delivers electrical signals to the vagus nerve, which transmits these messages to the brain [2].The stimulation engages a network of neural pathways that connect the brainstem to multiple regions of the brain [2]. Consequently, brain plasticity is increased, and a parasympathetic state is promoted, helping to alleviate pain [2]. One of the ways VNS efficiency was tested was by comparing it to a sham treatment [4-5,7-8]. Each of the studies that conducted this experiment found that VNS was significantly more effective than the sham treatment in easing migraine pain and, at times, relieving the pain altogether [4-5,7-8]. Furthermore, the studies showed that VNS patients experienced notably fewer attack days than those who received the sham treatment [4-5]. The consistently strong performance of VNS throughout these studies emphasizes that it is a reliable and functional treatment for migraines [4-5]. Given the high world-wide prevalence of migraines, it is imperative that new and effective treatments for migraines are explored [1]. Each of the studies was conducted in varying parts of the world, allowing for a diverse ethnic demographic of patients [4-8]. Study one was conducted in the Second Affiliated Hospital of Guangzhou University of Chinese Medicine [4]. Study two was held in the Taipei Medical University of Taiwan [5]. Study three took place in the Headache Center of the Carlo Besta Neurological Institute Foundation in Milan and the Headache and Pain Unit of the IRCCS San Raffaele Pisana in Rome, Italy [6]. Lastly, the fourth and fifth studies were conducted across ten Italian sites, whose details are not specified in the articles [7,8]. The diversity of these locations adds to the depth of these studies, further supporting the effectiveness of VNS [4-8]. All participants were aged 18 to 75 years, and while this range is relatively wide, none of the patients were minors [4-8]. This is important to note because migraines affect many young people, often beginning during puberty [1]. Future VNS studies should include patients of younger ages to see how the treatment impacts developing physiology. Overall, VNS is an impactful treatment for migraines, and the knowledge gained from future studies will continue to strengthen its effectiveness [4-8].