Effectiveness of Manual Trigger Point Therapy in Patients with Myofascial Trigger Points in the Orofacial Region—A Systematic Review

The objective was to compile, synthetize, and evaluate the quality of the evidence from randomized controlled trials (RCTs) regarding the effectiveness of manual trigger point therapy in the orofacial area in patients with or without orofacial pain. This project was registered in PROSPERO and follows the PRISMA guidelines. Searches (20 April 2021) were conducted in six databases for RCTs involving adults with active or latent myofascial trigger points (mTrPs) in the orofacial area. The data were extracted by two independent assessors. Four studies were included. According to the GRADE approach, the overall quality/certainty of the evidence was very low due to the high risk of bias of the studies included. Manual trigger point therapy showed no clear advantage over other conservative treatments. However, it was found to be an equally effective and safe therapy for individuals with myofascial trigger points in the orofacial region and better than control groups. This systematic review revealed a limited number of RCTs conducted with patients with mTrPs in the orofacial area and the methodological limitations of those RCTs. Rigorous, well-designed RCTs are still needed in this field.


Introduction
Myofascial trigger points (mTrPs) can be defined as hypersensitive or tender spots located within stretched muscle fibers (taut bands) of the skeletal muscles, which when compressed or stretched can cause referred or local pain [1]. Myofascial trigger points are associated with myofascial pain syndrome [1]. Myofascial pain can be defined as regional muscle pain that has increased pain sensitivity when palpated [2]. Myofascial pain and mTrP are commonly associated with orofacial pain and specifically associated with temporomandibular disorders (TMD), which are characterized by pain, reduced mouth Life 2023, 13, 336 4 of 28 of each study. The data extraction contained qualitative and quantitative elements. The following qualitative elements were extracted: article information; main objective of the study, study design, type of interventions, study setting, population, diagnosis tools, data collection methods, RCT type, number of randomized groups; outcomes; data analysis, results, conclusions, limitations, among others. The quantitative elements for treatment effect estimates were extracted for outcomes at baseline and at different time points, including mean, standard deviation (SD), sample size, standard error (SE), and confidence intervals. Any disagreements on data extraction were resolved by consensus.

Risk of Bias (Quality Assessment)
Quality assessment (risk of bias-RoB) was conducted by two independent reviewers on all included studies using the new risk of bias tool (RoB2) recommended by the Cochrane Collaboration [41,42]. Two reviewers independently assessed the RoB in the primary studies [43]. For the overall assessment of the RoB for each study, studies were rated as follows: "high risk of bias" (if the study was rated high in at least one domain), "some concerns" (if the study was rated as "some concerns" in at least one domain and the other domains were low), or "low risk of bias" (if the study was rated as low risk in all individual domains). Similar decision rules have been used by previous studies when rating the overall risk of bias assessment of RCTs [44]. Disagreements in risk assessment ratings were resolved by consensus. In addition, we used a compiled set of items from seven scales used to evaluate the RoB in the physical therapy field [45]. This compiled set of items has been described previously and has been used in several systematic reviews of our team [12,13,46].

Data Synthesis
We summarized our findings using a narrative synthesis based on the type of intervention (e.g., ischemic compression, myofascial release, trigger point pressure release), type of diagnosis (e.g., latent or not latent masticatory mTrPs), and based on the type of outcome (e.g., pain intensity, maximum mouth opening, and pain pressure threshold). We presented the study results using evidence tables and forest plots when feasible. We used forest plots to visually show study results and direction of the treatment effects. Narrative and qualitative summaries were provided when possible. Revman 5.4 software was used to construct forest plots for all comparisons. Mean differences (MD) were used to analyze continuous outcomes and ordinal data were analyzed as continuous data. To interpret MD, the minimal important difference was used for each of the outcomes. To interpret the pain intensity, mouth opening, and tenderness, a mean difference of 1.9 cm [47], 5 mm [48], and 1.12 Kg/cm 2 [49], respectively, were considered a clinically significant finding for these outcomes.
Overall Quality of the Evidence: The evidence was classified as high, moderate, low, and very low based on the GRADE approach based on the outcomes of interest [50]. The evidence was downgraded by one or two points when serious or very serious limitations, respectively, were found in the following domains: risk of bias, consistency of results, indirectness (reproducible, targeted to the population of interest), imprecision (insufficient data), or publication bias [50]. The evidence was upgraded based on three factors when applicable: large effect (up to 2 points increase), dose-response gradient (1-point increase), and plausible confounding that would change the effect.

Study Selection
A total number of 8483 studies were found in the databases. Twenty-four studies were selected for full-text screening; however, among those, 20 studies were excluded based on the reasons described in the PRISMA flowchart ( Figure 1). A detailed list of excluded studies and reasons for exclusion can be obtained from the authors upon request. Four Life 2023, 13, 336 5 of 28 studies were selected for data extraction and risk of bias assessment and were included in this systematic review [17,[51][52][53]. based on the reasons described in the PRISMA flowchart ( Figure 1). A detailed list of excluded studies and reasons for exclusion can be obtained from the authors upon request. Four studies were selected for data extraction and risk of bias assessment and were included in this systematic review. [17,[51][52][53] Table 1 summarizes the type of treatment, outcomes, results, and conclusions of each study. Regarding the diagnosis, two studies [17,53] included subjects with the diagnosis of trigger points and myogenic TMD using the RDC/TMD criteria [54] and two [51,52] included subjects with the diagnosis of latent mTrPs in the masseter muscles as stated by Simons et al. [2] but no OFP was identified by the authors.

Study Characteristics-Synthesis of Results
In terms of manual trigger points techniques, two studies [51,52] used the strain/counterstrain technique to treat latent mTrPs, and two studies [37,55] used ischemic compression to treat patients with myogenic TMD.
The duration of the sessions and exposure times, as well as the duration of the whole treatment (in weeks) were poorly described in all studies. No adverse effects were described in any of the included studies. No other outcome was used besides the ones presented in Table 1 (i.e., pain intensity, pressure pain threshold, maximum/active mouth opening, and range of motion for active knee extension). The timing of outcome measurements was carried out immediately after each intervention in all four studies. No followup analysis was performed.
The results and characteristics of the studies are shown in detail in Appendix D. Meta-analysis was not possible due to the low number of studies and heterogeneity among the protocols.  Table 1 summarizes the type of treatment, outcomes, results, and conclusions of each study. Regarding the diagnosis, two studies [17,53] included subjects with the diagnosis of trigger points and myogenic TMD using the RDC/TMD criteria [54] and two [51,52] included subjects with the diagnosis of latent mTrPs in the masseter muscles as stated by Simons et al. [2] but no OFP was identified by the authors.  In terms of manual trigger points techniques, two studies [51,52] used the strain/ counterstrain technique to treat latent mTrPs, and two studies [37,55] used ischemic compression to treat patients with myogenic TMD.

Study Characteristics-Synthesis of Results
The duration of the sessions and exposure times, as well as the duration of the whole treatment (in weeks) were poorly described in all studies. No adverse effects were described in any of the included studies. No other outcome was used besides the ones presented in Table 1 (i.e., pain intensity, pressure pain threshold, maximum/active mouth opening, and range of motion for active knee extension). The timing of outcome measurements was carried out immediately after each intervention in all four studies. No follow-up analysis was performed.
The results and characteristics of the studies are shown in detail in Appendix D. Metaanalysis was not possible due to the low number of studies and heterogeneity among the protocols.

Pain Intensity
Comparison of manual trigger point therapy vs. control group: Only one study [52] evaluated the effect of a manual trigger point technique (strain/counterstrain technique) compared to a control group. The qualitative comparison presented in the forest plot ( Figure 2) and Table 2

Comparison of manual trigger point therapy vs. other therapies:
Three of the studies [17,52,53] evaluated the effect of manual trigger point techniques (strain/counterstrain technique and ischemic compression) versus other interventions such as neuromuscular technique, [52] ischemic compression plus stretching of the hamstring, [53] kinesiotaping [17] to reduce pain provoked by TrPs. Based on the qualitative analyses, no significant differences in pain intensity favoring manual trigger point therapies versus other passive treatments were found. Kinesiotaping was found to be potentially clinically relevant based on the minimal important difference found between groups (MD [95% CI] −1.30 cm [−2.05, −0.55]) [47] (Figure 2 and Table 2 (Effect size)).

Pressure Pain Threshold
Comparison of manual trigger point therapy vs. control group: One study [52] evaluated the effect of a manual trigger point technique (strain/counterstrain technique) compared to a control group (i.e., no treatment). The forest plot ( Figure 2) and  [52], or hamstring stretching [53]. There were no significant differences between groups for pressure pain threshold values in both studies (Table 1 and Figure 2) [49].   [17,51,53]. All studies were considered to have high risk of bias overall. (b) Both studies used control groups without receiving any treatment, and the same treatment method for manual TrP therapy (strain/ counterstrain technique). Both studies investigated the effect of manual TrP on patients with latent myofascial TrPs in the masseter muscle. However, a high heterogeneity was obtained in the effect estimates.   (Figure 2, 2.3.6). Results of these studies were mixed; one study [51] found no statistical difference between groups and the other [52] found significant results favoring the manual trigger point therapy group. This study showed a clinically relevant increase on maximal mouth opening in the manual trigger point therapy group compared to the control group (MD [95% CI]: 6.00 mm [1.97, 10.03]) ( Figure 2).
Comparison of manual trigger point therapy vs. other therapies: Three studies [51-53] evaluated the effect of strain/counterstrain technique or ischemic compression versus other intervention methods such as post-isometric relaxation [51], neuromuscular technique [52], or hamstring stretching [53]. None of the studies showed a clear and significant difference between manual trigger point therapy and any of the other techniques analyzed (Figure 2 and Table 1).

Risk of Bias of Analyzed Studies
The risk of bias (RoB) is summarized in detail in Appendix E and Figure 3. All the included studies for this systematic review used a random sequence generation, provided well defined inclusion and exclusion criteria for their populations, and gave a detailed description of the protocols used for treatment. However, all of them had some methodological flaws (Appendix E). Questions regarding the interventions revealed that the treatment protocol was inadequately described by all included studies, as some details of exposure were not reported. Therefore, the reproducibility of these interventions is not possible.  Regarding all aspects of the compiled set of items and the RoB assessment tool, the four studies included in this systematic review were considered to have an overall high risk RoB (Figures 3 and 4, and Appendix E).

Quality of Evidence
The study quality was assessed using the GRADE approach. [50] The overall quality of evidence was very low (Table 2) due to the high RoB of all included studies and due to

Quality of Evidence
The study quality was assessed using the GRADE approach [50]. The overall quality of evidence was very low (Table 2) due to the high RoB of all included studies and due to the indirectness in some of the comparisons in this systematic review. The evidence was generally downgraded for three reasons including RoB, imprecision, and indirectness of the reported results.

Discussion
The findings from this systematic review show that manual trigger point therapy could potentially be beneficial for patients with mTrPs in the orofacial area. Even though manual trigger point therapy did not show a clear advantage over other conservative treatments, it was found to be an effective therapy for patients with mTrPs in the orofacial area and better than control groups. However, the number of studies was limited, the RoB was high, and the certainty of evidence was low. Despite the poor quality of the evidence, the non-invasive nature of the manual myofascial techniques can be an attractive complement or even alternative to other interventions. In addition, although we aimed to pool studies, this was not possible due to the heterogeneity of the results of the included studies.

Effectiveness of Manual Trigger Point Therapy in Comparison with Other Reviews
This systematic review results are in agreement with other systematic reviews focusing on other regions of the body, such as headache or neck pain, and myofascial pain syndromes [24,25,56]. All reviews agree that treatment with manual trigger point therapy techniques leads to a significant or promising improvement in several outcomes when compared with home exercises [57], physical therapy modalities (i.e., hot packs, transcutaneous electric nerve stimulation (TENS), stretch with spray, and others) [58], or transverse friction massage [59], but the level of evidence remains low to very low. Although previous reviews on this topic are available, they are already outdated (in the view of the Cochrane collaboration), as they were published more than 5 years ago, their conclusions can be maintained as their results agree with ours, which provides an updated analysis of this literature.
One finding of clinical importance from these reviews is that the included trials in these reviews had a low number of sessions or they did not implement follow-ups of the manual therapy treatment, similar to the findings of this systematic review. It is unlikely that short treatment exposure from these manual TrPs techniques (i.e., a limited number of sessions) can produce a significant and long-lasting effect as highlighted by our review.

Methodological Biases and Evidence Quality
As shown previously, all the included studies were considered to have a high risk of bias ( Figure 3). These common biases in the included studies could have impacted the results of this review and are shown in Figure 4. The lack of blinding might have influenced the results of the analyzed studies, but due to the nature of the treatment methods used, blinding might not have been possible in all cases. There are some strategies that have been suggested to overcome lack of blinding in this type of studies that could be used in future research in this area [60]. Even though the studies reported the interventions they used adequately for their treatment groups, they did not report on co-interventions, adverse effects, or adequate adherence to the treatments. In addition, it is unclear whether the participants received all scheduled treatment sessions and whether they received a sufficient dose of treatments, especially since some of the included studies [51,53] used only one session of manual trigger point therapy (Tables 1 and 2). Furthermore, none of the trials investigated any short-term or long-term effects of the interventions (no follow-ups). All these shortcomings make the evidence from these studies uncertain and poor.

Future Directions
This review shows that there is a paucity of studies looking at the effectiveness of manual trigger point therapy in individuals with myofascial trigger points in the orofacial region. In addition, from the few studies included, no high-quality evidence could be found, which indicates that there is great uncertainty about the effectiveness of manual trigger point therapy in comparison with other therapies in this area. There is a great need for well-designed RCTs considering the limitations highlighted by this review (see section above) to specifically investigate manual trigger point therapy for patients with mTrPs in the orofacial area [23][24][25].

Clinical and Research Implications
One of the striking results of this systematic review was that manual trigger point therapy techniques were only applied in a few sessions and were not followed up. Further studies are needed to examine the effect of manual trigger point therapy involving a longer period (more sessions) and measure the long-term effects of these interventions, especially the ischemic compression and strain/counterstrain techniques.
Surprisingly, none of the studies included in this systematic review used a placebo group. Thus, it is unclear, whether manual trigger point therapy was better than a placebo treatment. Future studies evaluating the effect of manual trigger point therapy techniques might need a stronger study design including a placebo intervention.

Strengths and Limitations of This Review
This systematic review has some strengths and limitations that need to be addressed at this point. The literature searches were performed by an experienced health sciences librarian. This enabled accurate identification of possible studies from the respective databases. In addition, our systematic review did not limit on the basis of language and we searched from 1946 to April 2021 (i.e., database inception to date of last search). Our inclusion criteria were also broad since our objective was to include all studies looking at manual trigger point therapies. Despite these broad criteria and the thorough search conducted, only four studies were found that met our criteria for inclusion. Furthermore, this review was the first to specifically investigate manual trigger point therapy in patients with latent mTrPs in muscles of the orofacial region. Nevertheless, the most common condition reported on was TMD.
In addition, it is important to note that a high risk of bias was found across all included studies, which limits the confidence of the effect of manual trigger point therapies. In addition, due to the paucity of the evidence (i.e., limited number of studies) as well as the heterogeneity of the literature (i.e., not used standardized protocols in the studies), no meta-analysis of the effect estimates could be performed. In addition, we could not explore publication biases through a funnel plot due to the limited number of studies. However, due to the comprehensive searches performed, we do not believe this is a concern.

Conclusions
The results from this systematic review support that strain/counterstrain therapy was superior to control groups for patients with mTrPs in the orofacial area to improve pain intensity, pain pressure threshold and mouth opening. However, manual trigger point therapy was equivalent to other active treatment techniques. Overall, the quality of evidence was very low and the risk of bias was high. Therefore, manual trigger point techniques could potentially be used as a complementary technique in the treatment of patients with mTrP in the orofacial area. In addition, there is a paucity of well conducted RCTs in patients with mTrPs in the orofacial region. Rigorous, well-designed RCTs are still needed in this field.
The manual trigger point therapy techniques targeted in this review will be the following: Ischemic compression: A manual therapeutic technique used in physical therapy, where blood is deliberately blocked in an area of the body, so that a resurgence of local blood flow will occur upon release. (1) Trigger point pressure release: Applying sustained pressure on a trigger point without inducing additional ischemia in trigger point zone. The amount of pressure applied should be enough to produce gradual relaxation of the tension within the trigger point zone, without causing pain. (2) Myofascial release: Myofascial release is a therapeutic method for stimulating connective tissue fibers. The treatment usually takes place locally on altered fascial structures and involves an application of a low load and long duration stretch. Myofascial release can be used to treat and especially decrease pain, restore optimal length of tissue and to improve the function. (3) Manual pressure on taut bands: Pressure, applied manually, on a myofascial trigger point, which is defined as a hyperirritable spot, usually within a taut band of skeletal muscle which is painful on compression. (4) Passive stretching: A passive stretch is one where the patient is asked to assume a position and hold it with the assistance of a therapist to stretch a determined muscle. The stretch is held until the stretched muscle tissue starts to relax. Passive stretch reduces muscle tissue stiffness, most likely by signaling connective tissue remodeling via fibroblasts (5,6).
Manual fascial techniques: The technique involves deep manual friction over specific points on the deep muscular fascia that are always at a distance from the actual site of pain (7).
Manual intraoral or extraoral release: The intraoral techniques usually involve applying digital pressure (known variously as ischemic compression, pressure release, myotherapy, or acupressure) into masticatory muscle trigger points, origins, or insertions, using intra-oral contact points. The extraoral technique applies the same digital pressure into the masticatory muscles but using extra-oral contact points (4).
Strain/counterstrain technique: This technique attempts to achieve the most comfortable position possible to relax muscle spasm by reducing abnormal afferent flow from the muscle spindle. If a myofascial trigger point is located in a muscle, a therapist applies gradually increasing pressure on that point until the feeling of pressure becomes a feeling of pressure and pain. Then there is a passive change of position of the patient performed by the therapist, until the tension under the palpating fingers and the pain reduces in intensity (8,9).      • Data expressed as mean and standard deviations or 95% confidence interval; • ANOVA test was used for continuous data to compare baseline values, and for categorical data, the X 2 tests were performed; • To evaluate changes after the interventions: Two-way mixed analysis of variance (ANOVA), using the time (pre-post test measurements) as the within-subject variable and group as between-subject variable; • The intention-to-treat analysis was used to analyze the subjects in the group to which they were allocated • Within groups: The effect sizes were calculated using the Cohen d coefficient; • The statistical analysis was conducted at a 95% confidence level and a p-value less than 0.05 was considered as statistically significant.

Limitations/Comments:
• Immediate effect of neuromuscular or strain/counterstrain techniques; • Participants had no symptoms and might not be typical for the population seeking manual therapy treatment.

Recommendations:
• Evaluate the long-term effect of the technique; • Include a placebo group; • Include participants with symptoms and complaints caused by myofascial TrPs. The treatments were not well described.

Recommendations:
• Include of a follow-up (medium and long-term); • Include athlete's performance level as participants.