Trigeminal neuralgia improvement following Transcutaneous Electrical Nerve Stimulation (TENS): a systematic review and meta-analysis

Abstract

Background

Trigeminal neuralgia (TN) is a prevalent and debilitating craniofacial pain disorder characterized by severe, unilateral, shock-like pain. Standard treatments include anti-epileptic drugs and surgical interventions, but many patients experience limited relief or adverse effects. Non-invasive therapies, such as transcutaneous electrical nerve stimulation (TENS), have emerged as alternative options. This systematic review and meta-analysis aimed to evaluate the efficacy of TENS in managing primary trigeminal neuralgia.

Methods

A comprehensive search of PubMed, Cochrane Library, and Google Scholar was conducted, yielding 89 papers. Following selection criteria, five clinical trials involving 101 patients with primary TN and TENS treatment were included. Data on pain severity, TENS parameters, and outcomes were extracted. Statistical analysis was performed using RevMan software, with outcomes assessed using Visual Analogue Scale (VAS) scores before and after TENS treatment.

Results

Pre-treatment VAS scores averaged 8.75 ± 0.18, indicating severe pain. Post-treatment, the mean VAS score significantly decreased to 1.17 ± 0.55, demonstrating substantial pain relief. The meta-analysis revealed a mean difference of 7.49 (95% CI: 7.05 to 7.93) in VAS scores, with a p-value < 0.05, indicating statistically significant pain reduction. Heterogeneity among studies was moderate (I² = 57%). Complications were infrequently reported, with one study noting paresthesia in a small number of patients.

Conclusion

TENS appears to be an effective and safe intervention for reducing pain in patients with primary trigeminal neuralgia. Despite variability in treatment protocols and follow-up periods, the overall evidence supports TENS as a viable option for managing TN pain. Future research should focus on standardizing TENS protocols and evaluating long-term efficacy and safety.

Introduction

Trigeminal neuralgia (TN) represents one of the most prevalent and debilitating forms of neuralgia within the craniofacial region [1]. This condition is typified by paroxysms of severe, shock-like pain that is described as sharp, stabbing, and penetrating. These episodes typically present unilaterally and affect one or more branches of the trigeminal nerve (cranial nerve V) [1, 2]. The pain experienced in TN is characterized by its sudden onset and cessation, with each episode generally lasting less than two minutes [3, 4]. The clinical manifestations of TN are notably heterogeneous, with variations in both the specific locations of pain and the duration of each episode among different patients. Furthermore, the condition is often precipitated by routine activities, such as chewing, speaking, brushing teeth, or washing the face [1, 5]. These triggers reflect the profound impact of TN on daily functioning and quality of life, highlighting its significance as a major concern in the field of neurology.

Statistical estimates regarding the prevalence of trigeminal neuralgia (TN) vary significantly, where Khan et al. reported it to be 1 in 25,000 individuals [6], while Ebrahimi et al. reported it to be 4 in 100,000 [7]. However, it is suggested that the actual prevalence of TN may be substantially higher than these figures indicate, potentially due to the existence of undiagnosed or misdiagnosed cases [1]. Additionally, TN appears to disproportionately affect females, with a female-to-male ratio of approximately 3:1 [8]. Research notes that TN is notably more common among individuals over the age of 50 [3, 7, 8].

Trigeminal neuralgia (TN) can arise from a range of mechanisms, encompassing peripheral pathologies such as root compression or traction, as well as dysfunctions involving the brainstem, basal ganglia, and cortical pain modulation systems [3]. Nevertheless, the neurovascular conflict theory is most widely endorsed. According to this theory, an artery or vein exerts pressure on the trigeminal nerve near the pons, resulting in myelin sheath damage and consequent erratic, hyperactive nerve function [9]. Additional contributing factors include focal arachnoid thickening, nerve angulation, adhesions, tethering, fibrous rings encircling the nerve root, cerebellopontine angle tumors, brainstem infarcts, aneurysms, and arteriovenous malformations [3].

Central mechanisms have also been implicated in TN. These include a reduction in μ-opioid receptors in the basal ganglia and alterations in gray matter within the sensory and motor cortices [10]. Such central abnormalities likely play a crucial role in the disease’s pathophysiology. Furthermore, the ignition hypothesis posits that demyelination and dysmyelination lead to increased electrical excitability, resulting in spontaneous and triggered ectopic impulses, as well as cross-excitation among adjacent afferent fibers [11]. On the other hand, the bioresonance hypothesis suggests that damage occurs when the vibrational frequencies of the nerve and its surrounding structures become closely aligned [12]. Additionally, the brain sagging or arterial elongation hypothesis proposes that these phenomena may contribute to nerve compression [9]. Regardless, the precise underlying pathophysiological mechanism is still unclear.

The diagnosis and management of trigeminal neuralgia (TN) are complex and necessitate a multi-disciplinary approach, including input from neurology, neurosurgery, oral and maxillofacial surgery, and oral medicine specialists [1, 6]. While several diagnostic tools are available, such as laser-evoked potentials (LEP) and magnetic resonance imaging (MRI), these alone cannot definitively diagnose TN. A thorough clinical interview with the patient remains essential for ruling out other differential diagnoses [1].

Treatment options for trigeminal neuralgia (TN) include both medication and surgery. Anti-epileptic drugs, with carbamazepine being the primary choice, are usually the first line of treatment [5]. Although carbamazepine is effective for many patients, it is only successful in 50–70% of cases and its effectiveness may diminish over time [1]. Unfortunately, it can cause side effects such as headache, dizziness, and nausea [4, 8].

For patients who do not respond to medication or have severe cases, surgical options may be considered. These include stereotactic radiosurgery, ganglion block surgery, percutaneous radiofrequency thermal rhizotomy, and microvascular decompression [1]. Surgery, while potentially effective, carries risks such as facial numbness, pain recurrence, and serious complications like cerebrospinal fluid leaks, infarction, and hearing loss. Surgical intervention is generally reserved for cases where medication fails or is poorly tolerated [13, 14].

Given the intricate nature of surgical and medical management plans, coupled with the often diminished patient adherence to these strategies, there has been a growing interest in non-invasive interventions such as transcutaneous electrical nerve stimulation (TENS) within the field of neurology [15]. TENS operates by employing electric currents to stimulate nerves, thereby mitigating pain. Research indicates that TENS is a promising and safe therapeutic modality for trigeminal neuralgia (TN), demonstrating enhanced patient compliance [15]. Hence, this systematic review and meta-analysis paper seeks to critically evaluate the efficacy of TENS in the management of trigeminal neuralgia.

Methodology

This systematic review and meta-analysis were conducted per the PRISMA guidelines [16].

Search strategy

A comprehensive search of three online databases (PubMed, Cochrane Library, and Google Scholar) was conducted on July 1^st 2024, using MeSh terms and keywords synonymous with “Transcutaneous electrical nerve stimulation” and “Trigeminal neuralgia”. Only papers published or professionally translated to English were included, with no limitations on publication date. Due to the study design of this paper, no institutional review board approval or patients’ informed consents were obtained.

Selection criteria

Papers were included if they complied with our study’s predefined PECOS of (P) individuals with a confirmed diagnosis of classical or idiopathic trigeminal neuralgia; (E) individuals that underwent a trial of TENS; (C) not applicable due to the complexity of TN; (O) reported pain on a standardized pain scale prior to and following TENS; (S) clinical trials. Exclusion criteria were: (P) individuals that had a diagnosis of secondary trigeminal neuralgia (secondary to multiple sclerosis, surgeries, herpes, neurosarcoid, etc.); (E) individuals that did not undergo TENS; (C) not applicable due to the complexity of TN; (O) studies that did not report their participants’ pain on a standardized pain scale prior to or following TENS; (S) any article that was not of a clinical trial design.

Study selection

Papers were screened for selection independently by two reviewers in two phases – an initial title and abstract screening followed by a full-text retrieval and screening. The inconsistencies were addressed by consulting a third reviewer.

Data extraction

Two reviewers performed data extraction independently using a pre-constructed Excel spreadsheet, with independent validation by a third reviewer. Discrepancies were resolved through discussion. The following items were extracted: author name, year of publication, number of patients, sex, age, duration of TN, severity of pain on a standardized scale before TENS, severity of pain on a standardized scale after TENS, mode of TENS used, duration of each TENS session, duration of the entire TENS trial, pulse width of TENS, frequency of TENS, remission, complications, and follow-up. Missing data were marked as not available (NA).

Risk of bias assessment

The risk of bias in this review was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) [17]. All bias assessments were performed and validated among authors.

Statistical analysis

The authors utilized Cochrane’s Review Manager (RevMan Version 5.4.1) to conduct this paper’s statistical analysis. Forest plots and funnel plots were constructed to illustrate the mean difference and publication bias assessment. The data type was set to be continuous, the confidence interval set for 95%, while the analysis mode utilized was ‘fixed effects’, and the effect measure was ‘mean difference’. A p-value of < 0.05 was considered statistically significant. In addition, the heterogeneity among studies was assessed using the chi-square, I², and Tau² tests. Lastly, pooled proportion meta-analyses were performed on eligible studies using the inverse variance method.

Primary and secondary outcomes

The primary outcome of this study is to assess the effect of TENS therapy on the VAS score in patients with classical or idiopathic TN. In addition, the secondary outcomes include the understanding of the side effects of TENS therapy, as well as the effects of different modes and durations of TENS on the patients.

Results

Descriptive summary

Our online database search yielded a total of 89 papers, of which 81 were chosen for title-abstract screening following the elimination of 8 duplicates. Of the 81 articles, 7 were assessed in full text, and 5 were included in the final analysis (Fig. 1).

Fig. 1

PRISMA flowchart filled out according to this study’s flow

A total of 101 participants with a confirmed diagnosis of classical or idiopathic trigeminal neuralgia underwent a trial of TENS. Of these, 41 were males and 60 were females. Regarding the age of the participants, the calculated mean and standard deviation of all participants were 55.11 ± 5.46. Additionally, the majority of participants experienced symptoms for extended periods. Yameen et al. recruited patients with at least 8 weeks of symptoms [18], Manning et al. reported a mean of 8 years [19], and Millan-Guerrero et al. reported a mean of 2.1 years [20]. The period of TN symptoms was not reported in either Bisla et al.’s or Singla et al.’s trials [21, 22].

The severity of pain was assessed using the Visual Analogue Score (VAS) – a scale ranging from 0 to 10 out of 10 – among all the studies included. VAS is a subjective measure of pain intensity per episode of pain [23]. The studies included measured the patients’ scaling of the pain intensity per TN episode or attack prior to and following TENS treatment. It is crucial to point out that the studies did not report the scores in between the sessions, only before and after the treatment; making the end-point score used in the analysis the one reported following the conduction of the TENS trials.

Before the TENS trials took place, the VAS score was reported to be 8.5 ± 2.92 in Yameen et al.’s trial [18], 8.66 in Manning et al.’s trial [19], 8.69 ± 1.123 in Bisla et al.’s trial [21], 8.9 ± 2.98 in Singla et al.’s trial [22], and 9 ± 1.33 in Millan-Guerrero’s trial [20]. Following the TENS trial, a potentially promising decrease in the reported VAS score was noticed. Yameen et al. reported it to be 2 ± 1.41 [18], Manning et al. reported it to be 1 [19], Bisla et al. reported it to be 1.23 ± 1.632 [21], Singla et al. reported it to be 1.3 ± 1.14 [22], and Millan-Guerrero reported it to be 0.3 ± 0.949 [20]. Before the TENS trials, the mean Visual Analogue Score (VAS) for pain was 8.75 ± 0.18, indicating a relatively high and consistent level of pain among participants. After the TENS trials, the mean VAS score decreased to 1.17 ± 0.55, reflecting a reduction in pain and greater variability in the reported scores. This substantial decrease in both mean and variability underscores the effectiveness of TENS in alleviating pain, as observed in the trials.

TENS has multiple modes that can be used in its operation. In Yameen et al.’s trial, 16 patients underwent a constant mode, while 15 underwent the burst mode [18]. In Manning et al.’s trial 3 patients underwent tonic mode, while 1 patient underwent the burst mode [19]. In Bisla et al.’s trial, all patients (26) underwent a continuous mode [21]. The modes used in TENS were not reported in either Singla et al.’s trial [22] or Millan-Guerrero et al.’s trial [20].

The duration of each TENS session was reported to be 30 min/week [18], 40 min/week [21], 20 min/day [22], and 60 min/week [20]. It was not reported in Manning et al.’s trial [19]. Regarding the duration of the entire TENS trial, it was reported to be 3 weeks in Yameen et al.’s trial [18], 1 year in Manning et al.’s trial [19], 6 weeks in Bisla et al.’s trial [21], and 1 year in Singla et al.’s trial [22]. It was not reported in Millan-Guerrero et al.’s trial [20].

The pulse width of the TENS device was reported to be 120u in Yameen et al.’s trial [18], 1000usec in Manning et al.’s trial [19], and 50-200us Millan-Guerrero et al.’s trial [20]. It was not reported in Singla et al.’s nor Bisla et al.’s trials [21, 22]. In addition, the frequency of the TENS device was reported to be 200 Hz in Yameen et al.’s trial [18], 40 Hz in Manning et al.’s trial [19], 100 Hz in Bisla et al.’s trial [21], and 50–200 Hz in Millan-Guerrero et al.’s trial [20]. It was not reported in Singla et al.’s trial [22]. Of note, remission of trigeminal neuralgia pain was not reported in any study except for Millan-Guerrero et al.’s. Surprisingly, at the 5-year follow-up, it was reported to be 7.1 ± 2.47 [20]. In addition, complications or adverse effects from TENS were not reported in Yameen et al.’s, Bisla et al.’s, or Millan-Guerrero et al.’s [18, 20, 21]. However, Singla et al. reported no occurrence of such events [22]. On the other hand, Manning et al. reported paresthesia to occur in three of their patients [19].

Lastly, the follow-up periods were reported to be at 3-month, 6-month, and 12-month intervals in Manning et al.’s study [19] as well as Bisla et al.’s trial [21]. Singla et al. reported them to be at 1-month and 3-month intervals [22]. In addition, Millan-Guerrero et al. reported them to be at 2-month, 3-month, 12-month, 3-year, and 5-year intervals [20]. Follow-up periods were not reported in Yameen et al.’s study [18]. All in all, the patients’ and trials’ characteristics can be seen in Table 1.

Table 1 Characteristics of the studies included and their participants

Statistical analysis

The meta-analysis showed a mean difference of 7.49 (95% CI: 7.05 to 7.93) in the VAS scores reported before and after the TENS intervention. The p-value for the overall effect of TENS intervention was < 0.05, making the results statistically significant.

Regarding the heterogeneity among the studies, the I² statistic was 57%, suggesting moderate heterogeneity among the included studies. The forest plot (Fig. 2) illustrates the individual study effects and the combined estimate of the mean difference. In addition, a funnel plot was conducted (Fig. 3) to assess the presence of publication biases. Our funnel plot shows a symmetrical distribution of points around the mean difference point, making publication bias unlikely to be present.

Fig. 2

Forest plot illustrating the individual study effects and the combined estimate of the mean difference

Fig. 3

Funnel plot of the included studies

Forest plot of the effect of TENS on pain reduction in trigeminal neuralgia. The plot shows the individual study results (point estimates and 95% confidence intervals) along with the overall pooled effect estimate. The center of each square represents the point estimate of pain reduction for each study, and the horizontal line indicates the confidence interval for that study. Larger studies are represented by larger squares, which indicate a higher weight in the meta-analysis. The diamond shape at the bottom represents the overall pooled estimate, with the center of the diamond indicating the overall effect of TENS on pain reduction and the width of the diamond representing the 95% confidence interval. The vertical line represents the line of no effect (zero for mean differences), with studies or the pooled estimate to the right of the line indicating a positive effect of TENS on pain reduction.

The funnel plot illustrates the effect of TENS on pain reduction in trigeminal neuralgia. The plot shows the relationship between the standard error on the y-axis and the mean difference in pain scores on the x-axis. Each point represents an individual study included in the meta-analysis. The vertical solid line marks the pooled effect estimate, while the dashed lines represent the 95% confidence interval of the overall effect estimate. The symmetrical distribution of studies around the vertical line suggests that there is no significant publication bias or small-study effects.

Discussion

The cornerstone of pharmacological treatment for trigeminal neuralgia is the use of antiepileptic drugs, with carbamazepine and oxcarbazepine being the first-line treatments. These medications function by modulating voltage-gated sodium channels, thereby reducing neuronal excitability and alleviating pain [24]. Despite their efficacy, these drugs can cause significant side effects, leading to treatment discontinuation or dosage reduction in many patients [25].

In addition to carbamazepine and oxcarbazepine, there is ongoing research into other pharmacological agents. Anticonvulsants as a class have shown success in managing TN, although there is a lack of high-quality studies that allow for comprehensive comparison or combination of results. Newer drugs, such as vixotrigine, are currently under investigation, offering hope for improved management of this condition [26].

Acute treatment for TN often involves hospitalization, where rapid-acting agents can be administered to manage severe pain episodes. Long-term management, however, typically relies on oral medications aimed at preventing pain attacks [27]. The complexity of TN treatment necessitates a personalized approach, taking into account the patient’s response to medication and the side effect profile.

While pharmacological treatments remain the first line of defense, nonpharmacological treatments have gained attention for their potential to alleviate symptoms without the side effects associated with medications. For example, repetitive transcranial magnetic stimulation (RTMS) is a non-invasive procedure that uses magnetic fields to stimulate nerve cells in the brain. It has been explored as a treatment for various neurological conditions, including TN. The mechanism involves altering the excitability of the brain’s cortical areas, which can modulate pain perception. Studies suggest that RTMS can provide temporary pain relief for TN patients, although the extent and duration of relief can vary significantly among individuals [28]. The application of RTMS for TN is still in the experimental stage, and more extensive clinical trials are needed to establish its efficacy and safety profile fully.

Other nonpharmacological approaches to TN include acupuncture, biofeedback, and physical therapy. Acupuncture, a traditional Chinese medicine technique, involves inserting thin needles into specific points on the body and has been reported to provide pain relief for some TN patients. Biofeedback, which teaches patients to control physiological functions such as muscle tension, may also help in managing TN symptoms by promoting relaxation and reducing stress. Physical therapy, including exercises and manual therapy, can help alleviate pain by improving muscle function and reducing tension in the facial muscles [29]. Nevertheless, TENS stands out among nonpharmacological treatments for several reasons. Firstly, it provides a non-invasive and drug-free option for pain management, which is particularly beneficial for patients who cannot tolerate or do not respond well to pharmacological treatments. Secondly, TENS units are portable and can be used at home, allowing for greater flexibility and convenience in managing pain [30]. Moreover, TENS has a low risk of side effects, which enhances its appeal as a long-term management strategy for chronic pain conditions like TN.

TENS alleviates pain through both peripheral and central mechanisms. Peripherally, it stimulates either large-diameter, low-threshold afferents (A-β) or small-diameter, high-threshold afferents (A-δ), reducing nociceptor activity and unwanted sensations [31, 32]. Molecular studies show that TENS modulates pain-related ion channels, like voltage-gated sodium channels, to inhibit nociceptor neurotransmission [33]. Centrally, TENS activates descending inhibitory pathways in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cord, decreasing pain signals in the dorsal horn [33]. High-frequency TENS increases β-endorphins and methionine-enkephalin, which interact with opioid receptors to lower glutamate and substance P release, potentially reducing central sensitization. Low-frequency TENS also engages GABA-A, muscarinic receptors, and serotonin [34]. The frequency of TENS affects receptor mediation: low-frequency treatments primarily activate μ-opioid receptors, while high-frequency treatments involve δ-opioid receptors, a distinction significant for opioid users as low-frequency TENS may be less effective [35]. Additionally, blocking peripheral α−2A adrenergic receptors can impair TENS analgesia [34]. Overall, TENS offers a versatile approach to pain management by engaging multiple pathways and receptors.

This systematic review and meta-analysis tackling the efficacy of TENS for primary trigeminal neuralgia provides valuable insights into its efficacy and application. The data analyzed indicate that TENS significantly reduces pain associated with this condition; with a possible similar real-life outcome in clinical settings. The initial Visual Analogue Scale (VAS) scores were high across studies, with an average pre-TENS score of 8.75 ± 0.18, reflecting severe pain levels among participants. Following TENS treatment, there was a substantial reduction in pain, with the post-TENS average VAS score decreasing to 1.17 ± 0.55. Such a decrease in dramatic pain levels reflects possible utilization of TENS in clinical settings in the future.

The variability in TENS application across studies—such as different modes (constant, burst, tonic), session durations, and trial lengths—reflects the diverse approaches used in managing trigeminal neuralgia. Although some trials, like those by Yameen et al. [18] and Manning et al. [19], used varied modes, the majority of trials demonstrated a significant reduction in pain regardless of the specific mode used. The lack of reported mode-specific efficacy suggests that while different modes may be utilized, they all contribute effectively to pain relief.

Duration and frequency of TENS treatment varied widely among studies. This variation highlights the need for standardized treatment protocols to better compare outcomes and optimize TENS application.

The pulse width and frequency settings of TENS devices also varied. These variations in settings may contribute to differences in individual responses to TENS, pointing to the necessity for further research to establish optimal parameters for TENS in treating trigeminal neuralgia.

The follow-up data reveal that while some studies reported outcomes up to 5 years, others had shorter follow-up periods or did not specify them. The long-term follow-up by Millan-Guerrero et al., which reported a VAS score of 7.1 ± 2.47 at 5 years [20], suggests that pain relief from TENS may not be permanent and could potentially return over time. This finding capitalizes on the need for ongoing management strategies and periodic reassessment of pain levels.

Complications related to TENS were infrequently reported. Singla et al. noted no adverse effects [22], whereas Manning et al. [19] reported paresthesia in a few patients. The absence of severe complications across most studies supports the safety profile of TENS. However, the variability in reporting adverse effects highlights the need for comprehensive documentation in future studies.

Studies with longer treatment durations and more frequent sessions tended to show more favorable outcomes. For instance, Manning et al. [19] and Singla et al. [22], with treatment periods of 1 year, reported better sustained pain relief compared to their counterpart shorter trials. The extended exposure to TENS in these longer trials likely allowed for a cumulative effect that contributed to greater pain reduction over time. Additionally, Manning et al. [19] and Millan-Guerrero et al. [20] included patients with longer symptom durations, which could make pain control more challenging. In addition, the mode of TENS applied also influenced the results. Burst mode, is known for providing rapid pain relief by delivering pulses in short bursts, which can stimulate endorphin release and override pain signals. This mode might have contributed to the more significant immediate reductions in pain in those studies, although Manning et al. [19] also reported some side effects like paresthesia. Continuous mode, used in Bisla et al.’s [21] trial, is typically better suited for chronic pain management, as it provides a constant level of stimulation, which may have been effective in the long-term relief of TN. On the other hand, tonic mode involves low-frequency stimulation and can help manage long-term pain but may not offer as rapid relief as burst or continuous modes.

In terms of stimulation parameters, pulse width and frequency played important roles in pain management. Higher pulse widths, may target deeper nerve fibers, potentially enhancing pain relief. Frequency also influences pain control. Studies that used frequencies in the moderate range (e.g., Bisla et al. [21] at 100 Hz) may have struck a balance between effective pain relief and minimal side effects.

The duration of TENS sessions and frequency of application also played a role in the overall efficacy. Studies that involved more frequent or longer TENS sessions per week likely saw more consistent pain relief due to the increased time the participants were exposed to the treatment.

All in all, studies with longer treatment durations, higher frequencies, and more frequent TENS sessions tended to show more favorable responses. The burst mode was most effective for immediate pain relief, while continuous or tonic modes appeared more suitable for long-term pain control, especially at moderate to low frequencies (40–100 Hz). The combination of these factors, along with sufficient treatment time and individualized adjustments based on the patient’s condition, appears to be key to achieving lasting pain relief in trigeminal neuralgia.

The meta-analysis further confirms the efficacy of TENS, with a mean difference of 7.49 in VAS scores before and after treatment, a result that is statistically significant (p < 0.05). The moderate heterogeneity (I² = 57%) suggests that while TENS is effective across studies, the variations in study design and implementation should be considered when interpreting results.

This paper has several limitations that affect the interpretation of TENS efficacy for primary trigeminal neuralgia. A primary limitation lies in the reporting of the VAS among the studies. The included studies report the VAS prior to and following the termination of the TENS trial; possibly hindering our understanding of possible variability or change trend in between the sessions themselves. Furthermore, another major limitation is the variability in TENS protocols across studies, including differences in modes, session durations, frequencies, and pulse widths. This inconsistency complicates efforts to standardize recommendations and directly compare results. Additionally, some studies did not report specific details such as the duration of TENS sessions or precise parameters used, which limits the ability to determine optimal settings and patient characteristics. The short follow-up periods in many studies, with some extending only up to 6 months, also restricts our understanding of the long-term benefits and potential recurrence of pain. Furthermore, the reporting of adverse effects was often inadequate, with only a few studies documenting complications like paresthesia, potentially underestimating the risks associated with TENS therapy. Another significant limitation is the lack of control groups in the studies, which impedes the ability to accurately attribute observed pain relief to TENS therapy rather than other factors such as natural disease progression or placebo effects. Still, it is understandable the complexity of including healthy patients as controls due to the presumed ineffectiveness of exposing them to TENS. The meta-analysis revealed moderate heterogeneity (I² = 57%) among studies, reflecting variability in study designs and outcome measures, which affects the generalizability and interpretation of the overall effect. Lastly, a major limitation is the assessment tool used. The visual analogue score (VAS) is a subjective measure and may be affected by an array of variables.

Despite these limitations, the review highlights several strengths of TENS treatment. The significant reduction in VAS scores across studies demonstrates that TENS may be an effective option in alleviating pain in patients with primary trigeminal neuralgia. The diverse study sample, which includes various genders and age groups, enhances the generalizability of the findings. The inclusion of multiple study designs, such as randomized controlled trials and observational studies, adds robustness to the evidence base, offering a comprehensive understanding of TENS efficacy. Notably, one study provided long-term follow-up data, which, despite showing some pain recurrence, is valuable for assessing the durability of TENS’s effects. Finally, the majority of studies reported no significant adverse effects, underscoring TENS’s favorable safety profile compared to more invasive treatments. Overall, while protocol variability and reporting inconsistencies pose challenges, the demonstrated pain reduction and safety profile underscore TENS’s potential as an effective and safe option for managing primary trigeminal neuralgia.

All in all, this review supports TENS as an effective and relatively safe intervention for managing pain in primary trigeminal neuralgia. However, standardization of treatment protocols, including mode, duration, frequency, and parameters, is needed to refine its application and enhance its efficacy. Further research with uniform methodologies and long-term follow-up is essential to optimize TENS treatment and understand its long-term effects on trigeminal neuralgia. Such research should include randomized clinical trials that further asses the possible benefit of utilizing TENS in neurological clinical settings.

Conclusion

This systematic review and meta-analysis provide robust evidence supporting the possible efficacy of transcutaneous electrical nerve stimulation (TENS) as a treatment for primary trigeminal neuralgia (TN). The significant reduction in pain, as evidenced by the decrease in Visual Analogue Scale (VAS) scores from an average of 8.75 ± 0.18 to 1.17 ± 0.55 following TENS therapy, underscores its effectiveness in managing TN symptoms. The meta-analysis further promotes that TENS can substantially alleviate pain, with a statistically significant mean difference of 7.49 (95% CI: 7.05 to 7.93) in VAS scores.

Despite the promising results, the variability in TENS application across studies—including differences in treatment modes, session durations, and device settings—highlights the need for standardized protocols to optimize treatment outcomes. The moderate heterogeneity (I² = 57%) among studies suggests that while TENS is generally effective, the variation in methodologies impacts the consistency of results. Additionally, the follow-up periods in many studies were limited, and complications were infrequently reported, indicating a need for longer-term studies and comprehensive adverse effect documentation.

In conclusion, TENS shows potential as a non-invasive option for managing primary trigeminal neuralgia, particularly for patients who do not achieve adequate relief from conventional treatments or prefer non-surgical interventions. Future research, preferably randomized controlled trials, should aim to standardize TENS treatment protocols, explore optimal parameters for efficacy, and assess long-term outcomes to further validate and refine its use in TN management.