The efficacy of intramuscular electrical stimulation in the management of patients with myofascial pain syndrome: a systematic review

Introduction Myofascial pain syndrome (MPS) is one of the most common disorders causing chronic muscle pain. Almost one-third of patients with musculoskeletal complaints meet the MPS criteria. The aim of this study is to evaluate the effectiveness of intramuscular electrical stimulation (IMES) in patients with MPS through a systematic review method. Methods PubMed, Scopus, Embase, ProQuest, PEDro, Web of Science, and CINAHL were systematically searched to find out the eligible articles without language limitations from 1990 to December 30, 2020. All relevant randomized controlled trials that compared the effectiveness of IMES with sham-IMES, dry needling, or exercise therapy in patients with MPS were included. Full texts of the selected studies were critically appraised using Revised Cochrane risk-of-bias tool for randomized trials (RoB2). Results Six studies (out of 397) had met our inclusion criteria (involving 158 patients) and were entered to the systematic review. Outcome measures examined in these studies included pain, range of motion, pressure pain threshold, biochemical factors, disability, and amount of analgesic use. In the most studies, it has been shown that IMES is more effective than the control group in improving some outcome measurements such as pain. Conclusion There is preliminary evidence from a few small trials suggesting the efficacy of IMES for the care of myofascial pain syndrome. The data support the conduct of larger trials investigating the efficacy of IMES. Supplementary Information The online version contains supplementary material available at 10.1186/s12998-021-00396-z.


Introduction
Myofascial pain syndrome (MPS) is one of the most frequent disorders causing chronic muscle pain that is usually overlooked [1]. Almost one-third of patients with musculoskeletal complaints meet the Simons and Travel MPS criteria [2]. Myofascial Pain Syndrome originates of effectiveness and long-term effects of physiotherapy interventions, including manual therapy, electrotherapy, and dry needling of TrPs. Therefore, it seems that further research is still needed to provide appropriate treatment for TrPs [8,13]. Based on previous study results, DN positively affects the signs and symptoms of MPS [10]. There is also some evidence that electrical stimulation (ES) can increase blood flow to the muscle [14,15]. Some researchers have combined DN with ES to achieve more effective treatment outcomes for blood flow, pain severity, and ROM, among others [16,17].
There is some evidence of the effectiveness of intramuscular electrical stimulation (IMES) applied to various body regions in patients with MPS; however, these studies have much heterogeneity, making it difficult to draw definitive conclusions and apply the results in clinical practice. Therefore, we conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of IMES in the management of patients with MPS.

Inclusion/exclusion criteria Type of studies
Any published RCTs reporting the effects of IMES on myofascial pain were included in this systematic review with no language restriction. Studies were considered eligible included patients with MPS based on Simons and Travel MPS criteria [2].
Also, only studies were included with patients with MPS.

Type of participants
Patients with MPS in any body region, sex, gender, and age were included.

Type of interventions
We include all RCTs applied IMES using DN with all types of wave properties. Anode or cathode use on TrP was not important for study including. All intervention types except IMES by DN, such as DN alone, ES insertion without DN use, or no intervention were considered proper for the control group.

Type of outcome measurements
Any quantitative outcome measurements like pain, ROM, functional disability score, etc., were accepted into the current study.

Search methods
Two researchers (MH & MJ) independently searched seven relevant databases to identify potentially relevant studies, including PubMed, Scopus, Embase, ProQuest, PEDro, Web of Science, and CINAHL from 1990 to December 2020. To identify keywords, the terms myofascial pain, trigger point, and intramuscular electrical stimulation were searched in medical subject heading (MeSH), and their synonyms were included in searching the databases. The searched keywords were ("Intramuscular electrical stimulation" OR "electrical intramuscular stimulation" OR "intramuscular stimulation" OR IMES OR EIMS OR "electrical twitch") AND ("trigger point" OR myofascial OR muscle OR muscular). The authors also searched the included articles' references and consulted the … University of Medical Sciences library to identify other relevant studies.

Study selection and data extraction
Two researchers (MH & MJ) independently screened the title and abstract of all identified articles. During the next stage, they reviewed the full texts of all potentially relevant studies. Researchers read the articles independently and extracted the data based on a pre-determined datasheet. The extracted data included study design, sample size, type of MPS disorder, age, interventions in experimental and control groups, number and frequency of treatment sessions, location of treatment, wave characteristics, needling method, outcome measures, and study results. We used Google Translate online software to extract data from non-English article [18,19].

Risk of bias assessment
We used Revised Cochrane risk-of-bias tool for randomized trials (RoB2) to evaluate the quality of included studies. This tool has five parts that include the Randomization process, Deviations from the intended interventions, Missing outcome data, Measurement of the outcome and Selection of the reported result. The overall bias for each study is based on the bias level obtained in each of these sections [20]. Any disagreements between the two researchers regarding the inclusion and quality assessment processes were resolved by an expert researcher (AR).

Statistical analysis
In this study, descriptive statistics are presented, including the means and SDs and statistical significance for between-groups comparisons for each outcome at each follow-up time point ("Appendix 1: Table 3"). Because of the small number of included studies and clinical heterogeneity discussed under the limitations section, data could not be pooled and meta-analysis on the results.

Results
After searching the databases and removing duplicate items, 397 potentially relevant titles and abstracts were identified. After screening the title and abstracts, 362 articles were excluded. Thirty-five studies were selected for full-text review. Finally, six studies were included in this systematic review based on the inclusion and exclusion criteria. The most frequent reasons for excluding studies were unrelated titles during the initial review, studies without electrical stimulation application via a needle, conference papers, etc. The details of the excluded studies with justification for exclusion are presented in the "Appendix 2: Table 4". The process of searching and screening is summarized in Fig. 1.

Characteristics of included studies
A summary of the methodological characteristics of the included studies and their results are presented in Table 1. Among the selected studies, five studies were in English [21][22][23][24][25], and one study was in Korean [26]. Two studies used patient and assessor blinding [22,24], and  two studies only used assessor blinding [21,23]. Two studies did not include any blinding [25,26]. Among the included studies, 76 and 82 patients were allocated to IMES and control groups, respectively. Three studies had parallel RCT designs with IMES and control groups [23][24][25]. Two other studies featured three parallel RCT designs. One compared the effectiveness of low-level laser therapy, IMES, vs. a control group [21]. Another included DN, IMES, and intramuscular stimulation (Gunn-IMS) groups [26]. One study had four groups, including repetitive Transcranial Magnetic
In three studies, sham-IMES groups were used as a control group [22][23][24]. In one study, participants in the control group received prescribed home-based exercises [21], while subjects in another two studies control group    [25,26]. The number of treatment sessions varied from one to ten sessions between studies.

Risk of bias assessment of selected articles
Among six included studies, two had low risk of bias [22,24] and three of them had moderate risk of bias [21,23,26]. The study by Brennan et al. [25] was the only study with high risk of bias due to inappropriate intention to treat analysis. Details of the study quality assessment are presented in Fig. 2. The details of the scoring of each item for the included studies are presented in the Additional file 1.

Wave properties and needle location in IMES group
In four studies, the upper trapezius muscle was treated [21,23,25,26]. Medeiros et al. and Botelho et al. applied IMES to the cervical paraspinal muscles [22,24]. Only three studies targeted trigger points [21,23,25]. The frequencies of the electrical stimulation ranged from 2 to 80 Hz. In two studies, the intensity was increased to the point of contraction [23,26]. Sumen et al. [21] increased the intensity until the patient sensed the stimulus. Three studies did not report any details about the intensity [22,24,25]. Wave properties and IMES technical characteristics are summarized in Table 2.

Outcome measures and summary of results
The visual analog scale (VAS) was the most common pain outcome measure. Three studies evaluated ROM measurements [21,23,26]. Other outcome measurements included pain by numeric pain rating scale (NPRS), pain pressure thresholds (PPT), biomarkers such as BDNF, pain or functional ability questionnaires, the neck disability index (NDI) and the McGill pain questionnaire (MPQ), and analgesic drug intake (Table 1). Also, the Details of included studies outcome measurements in assessment times (means with standard deviations) are presented in the "Appendix 1: Table 3". Byeon et al. [26] compared the effectiveness of IMES and DN; they showed improvement in pain and cervical lateral flexion ROM in all groups, but there were no significant differences of all outcome measurements in all assessment times in both groups [26]. Sumen et al. 's [21] results present statistically significant VAS decreases and PPT increases in the IMES group vs. the control group. Medeiros et al. [22] showed a significant difference in pain reduction between the IMES and control groups but no change in peripheral biomarkers parameters in the experimental and control groups. Hadizadeh et al. [23] showed that ROM was significantly higher in the IMES group than the control group one week after treatment. There were no significant differences in pain in all assessment times between both groups. Botelho et al. [24] showed a significant improvement in pain and analgesic drugs in the IMES group compared to the control group. Brennan et al. [25] compared the effectiveness of IMES and DN; they showed a significant improvement in pain and disability index in both groups and did not NDI or NPRS differ significantly between groups in any assessment times.

Discussion
The current study is the first systematic review evaluating IMES's effectiveness in patients with MPS to the best of our knowledge. Six studies with a total of 158 subjects were included in this review. Pain, the most common outcome measurement, was assessed by the VAS and NPRS or the MPQ. The effectiveness of IMES was compared with sham IMES, DN, or no intervention. The number of sessions varied from 1 to 10 sessions. The duration of IMES ranged from 10 to 20 min. The study by Hadizadeh et al. [23] was the only study with a single-session intervention. Three articles reported following the patients from 1 to 6 weeks [21,23,25,26].
In general, studies with a low risk of bias showed a significant improvement in the variables of pain, disability and analgesic use in the IMES group compared to the control group [22,24]. Also, in studies with moderate risk of bias (Some concerns), reduced pain and improved range of motion have been reported. However, in some cases, there was no significant difference with the control group [21,23,26]. In a study with a high risk of bias, no significant difference was reported between the IMES group and the control group in the variables of pain and disability [25].
Initially, we aimed to determine what factors would impact the effectiveness of IMES on MPS, such as the frequency of the applied currents, the duration, the exact location of active and reference needles or electrodes, among others, but the limited number of studies and the heterogenicity among studies did not allow for this kind of analysis. The study by Hadizadeh et al. was the only study demonstrating that one session of IMES could effectively reduce pain and increase ROM not immediately but after a one-week follow-up. It can be due to inflammatory processes after needle insertion, which may present as muscle soreness [27]. How many IMES sessions would be sufficient for clinical improvement cannot be deduced from the current research and requires further study.
There are some mechanisms explaining trigger points. One explanation is offered by the integrated hypothesis, which maintains that trigger points result from repetitive low-intensity trauma, leading to sarcoplasmic retinaculum injury, increased calcium concentration, and permanent contraction in the area. This would result in hypoxia and cell damage in the region [28][29][30]. It seems that surface, motor excitable electrical stimulation can increase the blood flow; therefore, it can decrease regional hypoxia. Commonly, IMES produces muscle contractions. This method can insert electrical stimulation to the depth of muscle with lower resistance against the current. Therefore, IMES seems to be more effective in managing regional hypoxia in TrP zone compared to superficial ES and the use of DN alone [15,31]. Besides, most studies used low-frequency current; low frequencies may cause the release of endorphins and enkephalins, leading to a reduction in pain [32].

Limitations
Our study has several limitations that should be mentioned. First, we included only primary RCT studies in this systematic review, which reduced the number of studies, limiting the ability to generalize the results of this study. Second limitation of this study is that, because the characteristics of the applied electrical stimulation like intensity, pulse duration, frequency, time, and etc. are not fully mentioned in all studies, it is not possible to make recommendations regarding the appropriate parameters. Third, we included RCTs with various type of interventions due to limitation in original studies. Fourth, the small number of included studies and clinical heterogeneity of included studies such as different fallow up point times, different sessions number, different control groups, and outcome measurements did not allow us to pool data and do a meta-analysis on the results. Further research is recommended to do a meta-analysis on this topic after further randomized controlled trials. Fifth, all of the included studies had a small sample size that can impact the result of the ROB2 tool. Therefore, the results of quality assessment in this study should be accepted with this limitation.
Further studies are needed to overcome these limitations. First, more RCT studies with larger sample sizes are needed to compare this intervention with other routine interventions. Second, studies are needed to investigate the placebo effects of this intervention. Studies with objective variables (like TrP size or stiffness found by radiologic methods) are also needed to evaluate this intervention's effectiveness. Also, future studies should include more detailed parameters of the interventions.

Conclusion
There is preliminary evidence from a few small trials suggesting the efficacy of IMES for the care of myofascial pain syndrome. The data support the conduct of larger trials investigating the efficacy and comparative effectiveness of IMES, and determining the optimal settings and dose of the intervention.