Effects of Electrical Stimulation on Facial Paralysis Recovery after Facial Nerve Injury: A Review on Preclinical and Clinical Studies

Various methods have been used to improve function and manage facial nerve injury. Although electrical stimulation therapy is frequently used to treat facial paralysis, its effects have been found to vary and no clear standards have been developed. The current review describes the results of preclinical and clinical studies evaluating the effectiveness of electrical stimulation therapy in promoting the recovery of a peripheral facial nerve injury. Evidence is presented showing the efficacy of electrical stimulation in promoting nerve regeneration after peripheral nerve injuries in both animal models and human patients. The ability of electrical stimulation to promote the recovery of facial paralysis was found to depend on the type of injury (compression or transection), the species of animal tested, the type of disease, the frequency and method of electrical stimulation, and the duration of the follow-up. Electrical stimulation, however, can also have potential negative outcomes, such as reinforcing synkinesis, including mistargeted axonal regrowth via inappropriate routes; excessive collateral axonal branching at the lesion site; and multiple innervations at neuromuscular junctions. Because of the inconsistencies among studies and the low quality of evidence, electrical stimulation therapy is not currently regarded as a primary treatment of facial paralysis in patients. However, understanding the effects of electrical stimulation, as determined in preclinical and clinical studies, is important for the potential validity of future research on electrical stimulation.


Introduction
The facial nerve is a mixed nerve that performs both motor and sensory functions. It is also mixed in the sense that it is a special sensory nerve that perceives taste in the anterior two-thirds of the tongue and is also a general sensory nerve responsible for the deep perception of the auricle, posterior wall of the external auditory meatus, ear lobe, and facial soft tissues [1,2]. Thus, the facial nerve consists of two efferent nerves and two afferent nerves and has four functions. Although facial nerve palsy is not a lifethreatening condition, the resulting facial asymmetry affects interpersonal relationships and imposes significant psychological and neurological stress on the patient [3]. The considerable socio-economic costs associated with the treatment and rehabilitation of facial paralysis underscore the importance of identifying the cause of facial paralysis and If the clinical outcomes of electrical stimulation in relation to facial paralysis are not favorable and have limitations, it would be beneficial to examine preclinical results and compare them with clinical results to understand the differences. Previous studies on electrical stimulation related to facial paralysis have not comprehensively reviewed both preclinical and clinical research. Therefore, in this study, we aim to investigate the potential efficacy of electrical stimulation in the treatment of facial nerve injuries by including both preclinical and clinical evidence. By comparing preclinical research findings with clinical outcomes, we can gain a better understanding of the differences and provide valuable insights into the effectiveness of electrical stimulation for facial paralysis. To the best of our knowledge, no previous study has conducted a combined review of preclinical and clinical research on electrical stimulation in relation to facial nerve injury. Hence, this review aims to bridge this gap and contribute to the existing literature by evaluating the potential benefits of electrical stimulation across both preclinical and clinical domains.

Methods
The current review included preclinical studies in animals and clinical trials in humans involving facial nerve injury and electrical stimulation. Studies examining recovery from facial nerve injury and the effects of electrical stimulation, published between January 1999 and September 2022, were retrieved from three electronic databases-PubMed, SCOPUS, and EMBASE-by one of the authors (M.C.Y) using the search terms, 'facial nerve', 'facial paralysis', 'recovery', 'Bell's palsy', 'electrical stimulation', and 'nerve regeneration'. Eligible studies were independently screened and the relevant data were extracted. If there was any uncertainty about whether to include a study, a second investigator (S.G.Y.) acted as an arbitrator and made the final determination. Studies were excluded if they were: (a) unrelated to the topic and could not compare the effects of electrical stimulation alone; (b) unpublished data; (c) duplicates of previously published research; (d) published in a language other than English; and (e) pilot studies.

Results
A total of 218 articles were obtained from the three databases using the specified search terms. However, only 22 studies (9.9%) met the inclusion criteria and were included in the analysis, as illustrated in Figure 1. The characteristics of these included studies are presented in Tables 1 and 2. stimulation improves recovery while others are concerned about the potential adverse effects and increased risks of synkinesis.
If the clinical outcomes of electrical stimulation in relation to facial paralysis are not favorable and have limitations, it would be beneficial to examine preclinical results and compare them with clinical results to understand the differences. Previous studies on electrical stimulation related to facial paralysis have not comprehensively reviewed both preclinical and clinical research. Therefore, in this study, we aim to investigate the potential efficacy of electrical stimulation in the treatment of facial nerve injuries by including both preclinical and clinical evidence. By comparing preclinical research findings with clinical outcomes, we can gain a better understanding of the differences and provide valuable insights into the effectiveness of electrical stimulation for facial paralysis. To the best of our knowledge, no previous study has conducted a combined review of preclinical and clinical research on electrical stimulation in relation to facial nerve injury. Hence, this review aims to bridge this gap and contribute to the existing literature by evaluating the potential benefits of electrical stimulation across both preclinical and clinical domains.

Methods
The current review included preclinical studies in animals and clinical trials in humans involving facial nerve injury and electrical stimulation. Studies examining recovery from facial nerve injury and the effects of electrical stimulation, published between January 1999 and September 2022, were retrieved from three electronic databases-PubMed, SCOPUS, and EMBASE-by one of the authors (M.C.Y) using the search terms, 'facial nerve', 'facial paralysis', 'recovery', 'Bell's palsy', 'electrical stimulation', and 'nerve regeneration'. Eligible studies were independently screened and the relevant data were extracted. If there was any uncertainty about whether to include a study, a second investigator (S.G.Y.) acted as an arbitrator and made the final determination. Studies were excluded if they were: (a) unrelated to the topic and could not compare the effects of electrical stimulation alone; (b) unpublished data; (c) duplicates of previously published research; (d) published in a language other than English; and (e) pilot studies.

Results
A total of 218 articles were obtained from the three databases using the specified search terms. However, only 22 studies (9.9%) met the inclusion criteria and were included in the analysis, as illustrated in Figure 1. The characteristics of these included studies are presented in Tables 1 and 2.

Parameters:
Facial muscle movement, compound muscle action potentials (CMAPs), Histological structure The expression levels of S100B and NF200.

Post-injury duration: 28 days
The ES group showed a higher amplitude and shorter latency of compound muscle action potential from day 14 to 28 after surgery, as well as increased number of axons and expression of S100B and NF200 proteins.
ES promotes outgrowth and myelination of axons and a partial functional recovery of facial muscles in rats with injured facial nerves. Location: first wire was looped around the proximal stump of the facial nerve. The second wire was imbedded into muscle tissue adjacent to the facial nerve. Performing BES after facial nerve injury is associated with accelerated facial nerve function and improved facial nerve specific pathway regeneration in a rat model. Location: first wire was looped around the proximal stump of the facial nerve. The second wire was imbedded into muscle tissue adjacent to the facial nerve.

Post-injury duration: 6 weeks
In rats subjected to facial nerve transection and neurorrhaphy at the main trunk of the facial nerve, those that received BES after transection showed significantly accelerated whisker movement compared with those that did not.

Post-injury duration: 30 days
Vibrissae movement returned significantly earlier on the ES side. Electrophysiologically, the stimulated side had a significantly shorter latency, longer duration, and faster conduction velocity.
Light and transmission electron microscopy revealed that the electrical stimulation also markedly decreased Wallerian degeneration.
Subthreshold, continuous, low-frequency ES immediately after a crush injury of the facial nerve results in earlier recovery of facial function and shorter overall recovery time.  ES or TP treatments enhanced recovery of some functional parameters more than P treatment.
A combinatorial treatment strategy of using ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury.     Adverse event: not specified The stimulation produced a blink in 8 participants (53%).
Electrically elicited blink is a promising method for reducing the eye symptoms in individuals with acute facial nerve palsy

Parameters:
Compound muscle action potentials (CMAPs) Latency of nerve action potential Sunnybrook facial grading system

Adverse event: not specified
Short-term investigation revealed that LLLT was more efficient than ES in facial nerve regeneration for patients with Bell's palsy.
There was no statistically significant difference between Group 2 and 3.
Puls et al., 2020 [41] Facial paralysis caused by surgical removal of benign or malignant tumor.
Hypoglossal-facial-jump anastomosis (HFJA) in the last 12 years were selected Retrospective study.

Adverse event: no
No difference in time of reinnervation after facial nerve reconstruction surgery was observed between patients who did and did not receive ES.
After spontaneous reinnervation, less synkinesis was noted.
There was no evidence that ES prevents or delays reinnervation or increases synkinesis in facial paralysis.

Parameters: Facial Disability Index
During the acute phase of Bell's palsy, the clinical effects of electrical stimulation were noticeable but did not reach statistical significance.

Animal Studies Reporting Effective Electrical Stimulation Results
Charge-balanced transcutaneous electrical nerve stimulation (cb-TENS), performed after facial nerve injection in Sprague-Dawley (SD) rats, was reported to achieve functional recovery of the facial nerve [24]. In these studies, a 2.5-cm incision was made to expose the facial nerve trunk at the front of the ear in male SD rats. The main trunk of the left facial nerve was then surgically excised 10 mm distal to the stylomastoid foramen and the nerve was immediately anastomosed with a single 9-0 nylon outer membrane suture. Rats were divided into three groups: control, electrical stimulation at 20 Hz, and electrical stimulation at 40 Hz groups. The control group (22 animals) underwent surgery but did not receive cb-TENS treatment. Whisker movement improved over time in all groups, including unstimulated controls. However, recovery tended to be faster and more complete in groups treated with cb-TENS compared with the control group, with results in the 40 Hz group exhibiting a significant difference relative to the controls on the seventh post-surgery day (p < 0.0125). Moreover, molecular analyses showed that levels of the pro-inflammatory cytokines, IL-1β and IL-6, were significantly higher in the 20-and 40-Hz groups than in the control group (p < 0.015). Collectively, these observations indicate that Cb-TENS promotes and accelerates the recovery of the facial nerve in a rat model, greatly reducing the time for the recovery of whisker movement [24].
In another study, Foecking et al. sought to investigate whether electrical stimulation immediately after a facial nerve crush injury could further reduce the time to fully recover from facial paralysis [29]. In the experimental groups, electrical stimulation was given as 1-ms-wide square wave direct current stimulus pulses at 20 Hz (1.5 mA, 1 s), followed by a 1-s rest period. Electrical stimulation significantly reduced the time to the first recovery of the eye blink reflex (p < 0.001); among animals receiving one, two, or four sessions of electrical stimulation, full recovery of the blink reflex was achieved in an average of 12.5 days compared with 17.0 days in the control group (~26% reduction). The delivery of electrical stimulation only once was as effective as delivering electrical stimulation multiple times; all groups that received electrical stimulation recovered full vibrissae movement faster than untreated animals (p < 0.05), with a single, short (30 min) electrical stimulation session immediately after facial nerve crush injury significantly reducing the time to complete functional recovery. These results suggest that in cases where surgeons identify facial nerve damage during a surgical procedure, muscle reinnervation could be increased by a single session of short electrical stimulation administered to the nerve prior to wound closure [29].
In a study employing 24 female Wistar rats that received a transection injury or a crush injury of the facial nerve, electrical stimulation of an implantable stimulator demonstrated good therapeutic effects [27]. Four groups of six rats underwent the facial nerve injury procedure. Rats in Groups 1 and 2 suffered crush injuries to the main trunk of the nerve and those in Group 2 received brief electrical stimulation (BES) for an additional 1 h. Rats in Groups 3 and 4 received a transection injury to the main trunk and rats in Group 4 received BES for an additional 1 h. After nerve injury, the first wire was looped around the proximal stump of the facial nerve and the second wire was inserted into the muscle tissue next to the facial nerve at a position immediately adjacent to the first wire. The insulated wire was connected to an isobaric stimulator that delivered a 1.5-mA current with a pulse of 100 µs in a continuous 20 Hz train for 1 h. Crush injury animals that were administered BES showed significantly greater whisking amplitude 2, 4, and 6 weeks after treatment (p < 0.05). Collectively, these findings indicate that performing BES after facial nerve injury is associated with the acceleration of facial nerve function and improved regeneration of the facial nerve-specific pathway in a rat model [27].

Animal Studies Reporting Ineffective Results of Electrical Stimulation
In some animal model studies, ineffective results of electrical stimulation for facial nerve injury were observed. Raslan et al. transected the right facial nerve in Wistar Unilever rats and electrically stimulated the proximal nerve cut for 60 min [34]. In the control animals, electrodes were immobilized on the nerve but no current was applied (sham stimulation). The operation was performed on the right facial nerve, with the application of electrical stimulation (n = 10) or sham stimulation (n = 9) during proximal nerve stump surgery. Motion analyses performed after facial injury showed poor vibrissal motion 4 weeks after sham stimulation. In the experimental group, whisking amplitude, velocity, and acceleration reached only 13-22% of that on the contralateral side at this same time point. This group showed a small improvement in the amplitude of agitation 8 weeks after injury; however, the velocity and acceleration were similar. For all parameters, values in the sham stimulation group were similar at 4 and 8 weeks after the injury. The authors of this study concluded that electrical stimulation may not be a universal treatment for facial nerve injury [34]. (Table 2) 3.

Human Studies Showing Effective Electrical Stimulation Results
There have been few large prospective randomized studies of electrical stimulation as a treatment method related to the recovery of facial palsy in humans. Kim et al. conducted a prospective randomized study involving a relatively large number (n = 60) of patients with mild to moderate Bell's palsy (House-Brackmann grade ≤ 4, Sunnybrook grade ≥ 40) to evaluate the effect of electrical stimulation on the resolution of facial palsy [17]. Thirty patients were treated with prednisolone and/or acyclovir and electrical stimulation within 7 days of symptom onset. Another 30 patients that were treated with only prednisolone and/or acyclovir were used as controls. The follow-up period was 1 year. Electrical stimulation was delivered with an electrical stimulator, which generated pulses with the following properties: average strength, 1.4 mA (sub-threshold); duration, 10 ms; interval, 50 ms; voltage, 10-20 V; frequency, 20 Hz with rectangular, monophasic spikes. All patients, except for one in the experimental group, were cured within 3 months. By contrast, five patients in the control group had not recovered normal facial function 6 months after the onset of paralysis. The facial function had fully recovered within 10.7 ± 5.7 weeks after the onset of facial paralysis in the experimental group compared with 13.4 ± 6.0 weeks in the control group. The experimental group showed an improvement in facial performance during the first 2 weeks and achieved complete recovery in a maximum of 10 weeks compared with 12 weeks for members of the control group, a difference that was significantly shorter (p < 0.05).
One year after the onset of facial paralysis, one patient in the experimental group showed synkinesis (oral-ocular synkinesis) accompanied by involuntary eye closure resulting from voluntary mouth movement, as well as static and dynamic facial asymmetry attributable to hypertonia, an unwanted secondary effect. Three patients in the control group showed an incomplete recovery of their facial function, all of whom also exhibited synchrony owing to secondary catatonia following facial paralysis. Sub-threshold continuous low-frequency electrical stimulation (SCLES) applied to the extratemporal part of the facial nerve immediately before the end of Wallerian degeneration resulted in a faster recovery of facial function and minimal facial sequelae after Bell's palsy, suggesting SCLES as a new treatment approach for accelerating nerve regeneration and improving functional recovery after injury [17].
In another study on Bell's palsy patients, in this case, a prospective study performed by Frigerio et al. [37], between 6 and 60 days in 40 patients with acute unilateral facial paralysis (House-Brackmann grades 4-6), electrical stimulation showed good therapeutic effects. Complete eye closure occurred in 55% of patients. In these individuals, initial eye twitching was observed at an average current of 4.6 ± 1.7 mA (average pulse width, 0.7 ms; frequency, 100-150 Hz) and complete eye closure was produced at an average stimulation strength of 7.2 ± 2.6 mA. Another study further revealed that the addition of 3 weeks of daily electrical stimulation shortly after the onset of facial palsy (4 weeks) improved functional facial movements [16]. Study participants were randomly divided into two equal groups: a conventional therapy group, treated with hot packs, facial expression exercises, and massages of the facial muscle and a group with conventional therapy plus concurrent electrical stimulation, performed 5 days per week for 3 weeks. In the control group, axonal degeneration was not detected in 16 patients (57.1%) but was found in 12 patients (42.9%). In the experimental group, 17 patients (53.1%) showed no evidence of axonal degeneration, whereas 15 (46.9%) exhibited axonal degeneration. The addition of daily electrical stimulation for 3 weeks within 4 weeks of the onset of facial paralysis improved measures of functional facial movement and electrophysiological outcomes in Bell's palsy patients at a 3-month follow-up [16].

Human Studies Showing Ineffective Electrical Stimulation Results
Some human studies have reported no effect of electrical stimulation, alone or in combination with conventional treatments, on facial nerve regeneration after facial nerve injury. In a prospective study investigating the therapeutic efficacy of electrical stimulation in Bell's palsy patients, patients in both the control group and the experimental group were treated with a 5-min hot compress, a 10-min massage, and ten repetitions of exercise three times a week [15]. The experimental group additionally received electrical stimulation to the facial muscles for 30 min, delivered using a TENS device. The Facial Disability Index (FDI) improved, on average, by 52.8% (from 17.8% to 95.4%) in the control group and 49.8% (from 14.8% to 126%) in the experimental group, a difference that was not statistically significant [15].
In a final study, electrical stimulation was attempted in six patients with sublingualfacial-jump anastomosis (HFJA) [41]. While waiting for reinnervation after HFJA, patients in the hospital practiced placing electrical stimulation electrodes with the help of a mirror and then were advised to perform home training twice a day for 10 min, 5 days per week. Six patients (three men and three women) received electrical stimulation and thirty-three patients (seventeen men and sixteen women) did not. No differences in the innervation time after facial nerve reconstruction were seen between patients with and without electrical stimulation. Moreover, no significant differences in eFACE scores for exercise and resting symmetry were found between electrical stimulation and no electrical stimulation in comparisons of absolute differences between healthy faces and the two groups. The authors concluded that there was no evidence that electrical stimulation prevented or delayed reinnervation or increased synthetic locomotion in facial paralysis patients [41].

Discussion
Bell's palsy is the most frequent form of facial paralysis encountered in clinical practice. Although around 70-80% of adults experience spontaneous recovery without treatment, some individuals may experience residual deficits [42,43]. These complications can include permanent facial paralysis, synkinesis (abnormal involuntary movements), muscle contracture, and facial asymmetry. Thus, patients with Bell's palsy are greatly concerned about its resolution and the risk of developing permanent paralysis.
Bell's palsy has traditionally been managed through a combination of physical and medical treatments. Physical treatment options have included massages, facial exercises, biofeedback, and electrical stimulation [13,44]. Although the effectiveness of the electrical stimulation for Bell's palsy is unclear, it is thought to have the potential to improve recovery in patients with poor prognostic factors. Electrical stimulation may enhance muscle and nerve function, expedite the healing process, and reduce the risk of long-term paralysis in patients with acute Bell's palsy [40]. Therefore, electrical stimulation is being explored as a physical therapy approach to improve this chronic condition; numerous preclinical and clinical studies have been performed to assess its effectiveness. For example, the continuous electrical stimulation of patients with chronic facial palsy for 6 months was reported to improve motor conduction latencies and clinical residuals, suggesting that prolonged electrical stimulation may facilitate reinnervation, potentially originating from neighboring healthy nerves, such as the fifth cranial nerve [38]. In addition, electrical stimulation-induced neuromodulation has been found to stimulate the remaining nerves, activating their inherent plasticity, which may lead to sensory and motor reorganization [45]. Continuous electrical afferent stimulation at a sub-sensory level has been reported to trigger a neurophysiological mechanism that can be activated by externally controlled sensory input, thereby inducing modulatory effects within the sensorimotor cortex [46].
Several studies, however, have reported insufficient evidence to adequately support the effectiveness of electrical stimulation in patients with facial paralysis. A 2011 Cochrane review on physical therapy for facial paralysis mentioned various treatment modalities, including exercise, biofeedback, laser treatment, and electrical therapy; however, it reported a lack of sufficient evidence to support their effectiveness [13]. Furthermore, contractions generated by electrical stimulation can further activate already overactive muscles and reinforce abnormal patterns [47,48]. Therefore, further research is needed to better understand the potential benefits and limitations of these treatment approaches.
Basic research experiments, coupled with the histopathological analysis of tissue samples, can enhance our understanding of the various mechanisms underlying the effects of electrical stimulation and provide valuable insights for improving patient prognosis (Table 1). Most preclinical studies in animal models tested the effectiveness of electrical stimulation by invasive insertion or wrapping electrodes. Electrical stimulation in rat models of crushed facial nerves has been shown to enhance the expression of regeneration-associated genes and proteins, such as brain-derived neurotrophic factor (BDNF), α1-tubulin, and growth-associated protein-43 (GAP-43) [31]. Electrical stimulation was also found to enhance the expression of cytokines and/or the release of neurotrophins, which play crucial roles in peripheral nerve regeneration and functional recovery [24,49]. Although several methods of stimulation, involving direct invasive insertion or implantation of electrodes, have shown efficacy in preclinical studies, the clinical applications of these methods are limited. Many preclinical studies have utilized surgically implanted stimulation devices, such as two Teflon-coated wires, which have limited applications in humans. Thus, the types, frequencies, and duration of electrical stimulation, as well as the quantitative methods of assessing recovery and the types of injury, have varied widely in preclinical studies, leading to heterogeneous results.
In most clinical studies, electrical stimulations were delivered transcutaneously (Table 2). Furthermore, the types of conditions varied among these studies, including Bell's palsy, acoustic neuroma excision, and hypoglossal-facial-jump anastomosis. Six of the studies tested found that electrical stimulation yielded positive results, whereas three studies found that electrical stimulation yielded no significant benefits. Most studies utilized electrical stimulations delivered at intensities sufficient to induce muscle contractions, with the exception of one study that used sub-sensory level stimulations [17]. Unfortunately, reporting on the adverse effects was inadequate or nonexistent. For future research, it is necessary to establish standardized protocols for electrical stimulation parameters, treatment duration, and evaluation methods. This standardization will enable meaningful comparisons among studies and facilitate meta-analyses to analyze the results. Furthermore, the potential adverse effects of synkinesis resulting from electrical stimulation should be considered in studies of patients with acute facial paralysis. It is crucial to investigate whether these adverse effects are exacerbated or alleviated by electrical stimulation. Additionally, studies are needed to determine the optimal duration of electrical stimulation and whether, and at what point, it should be continued or discontinued.
This review provides an overview of preclinical studies conducted primarily in rodent models and human research findings. Rodent models, commonly used in preclinical studies, have advantages, such as small size and suitability for experimental nerve repair. However, data obtained from these models should be critically evaluated. Interpretation of the results from preclinical and clinical studies should take into consideration the excellent regenerative capacity and smaller limb length observed in small animal models, particularly in mice [50]. Selecting a consistent and appropriate time point for evaluating facial nerve regeneration and functional recovery in mouse experiments is of utmost importance. This is particularly crucial in order to prevent data distortion and bias, ensuring the reliability of the results [50]. Additionally, aligning the findings from mouse experiments with those obtained from larger animal models can provide further validation and strengthen the translational potential of basic research on nerve regeneration in clinical applications.
The application of electrical stimulation in all facial paralysis patients primarily focuses on addressing facial weakness and preventing further damage on the affected side. However, in the context of emerging technologies, there is ongoing research on methods where electrical stimulation is induced by the contralateral side of the face. This approach involves recording signals from healthy neural tissue to extract neural signals that are then used to treat the damaged side of the face. Implants equipped with flexible muscle stimulation electrodes and electromyographic recording arrays have been used, along with a portable pulse generator, to capture and stimulate symmetric facial movements [51]. There are various types of electrodes used for neural stimulation. These include extra-neural electrodes, such as cuff electrodes and flat interface nerve electrodes (FINE), as well as intraneural electrodes, such as longitudinal intra-fascicular electrodes (LIFE), transverse intra-fascicular multichannel electrodes (TIME), and multielectrode arrays. Furthermore, these technologies allow for the connection of individual wires to percutaneous connectors or implantable wireless interfaces, enabling recording or electrical stimulation of the facial nerves [52,53]. The advancement of bioelectrical interfaces and nanotechnology holds the potential to expand the possibilities for successful therapeutic interventions in future research. These advancements can contribute to restoring lost neural inputs and facilitating muscle function recovery.

Conclusions
Despite a long history of peripheral nerve electrode development, commercialization remains limited and standard surgical methods have yet to be established; although, dataassessing factors that contribute to the failure of different clinical applications continue to accumulate. The effect of electrical stimulation on the regeneration process after facial nerve injury depends on the cause of facial paralysis, the degree of damage, the method of electrical stimulation, the number of stimuli used, and the follow-up period; for animal studies, the method used to induce the injury and the type of animal are contributing factors. Reports on the ability of electrical stimulation to promote recovery from facial paralysis have yielded varying results; the current review indicates that the therapeutic efficacy of electrical stimulation differs between humans and animals. The effectiveness of electrical stimulation in patients with facial nerve damage caused by viral reactivation, trauma, and benign and malignant tumors, as well as the resulting facial paralysis, may differ from its effectiveness in preclinical studies in animals with artificial damage. However, the preclinical and clinical studies described in this review provide clues to the possible ranges of electrical stimulation for optimal facial nerve treatment. More detailed and objective future studies on the effects of electrical stimulation on facial nerve regeneration after facial nerve injury are needed to determine optimal facial nerve treatments.