BotulinumtoxintypeAforthetreatmentofheadandneckchronicmyofascialpainsyndrome:Asystematicreviewandmeta-analysis

Myofascial pain syndrome (MPS) is a widespread health problem affecting approximately 85% of the general population at some point in their lifetime, with an overall prevalence of about 46%. Patients with MPS experience pain, mood changes, varying levels of physical disability, and reduced quality of life. The syndrome is characterized by myofascial trigger points located in contracted knots within tense muscle fibers. One treatment option being studied is the injection of botulinum toxin type A (BoTN-A) into trigger points.

BoTN-A inhibits the release of acetylcholine from nerve endings, causing muscle paralysis, and may also inhibit the release of nociceptive mediators such as substance P and glutamate. However, the effectiveness of this treatment has not been well established due to lack of standardization, different doses, and varying outcomes across studies. This systematic review and meta-analysis was designed to analyze randomized controlled trials regarding the efficacy of BoTN-A injection at active trigger points for treating MPS in the head and neck region.

The authors conducted a comprehensive systematic review with meta-analysis following Cochrane Collaboration and PRISMA guidelines. They searched three electronic databases (PubMed/MEDLINE, Web of Science, and the Cochrane Library) through June 1, 2016, for randomized, double-masked, placebo-controlled studies. The initial search yielded 319 records plus 1 additional record from manual searching. After removing duplicates and screening titles and abstracts, they identified 16 relevant manuscripts.

Three reviewers independently assessed studies for inclusion and risk of bias using the Cochrane risk of bias tool. They excluded studies that were not RCTs, lacked a placebo group, were case reports, animal studies, reviews, or had other methodological limitations. Ultimately, 13 studies were included in the qualitative synthesis and 11 studies in the meta-analyses. The primary outcome was pain reduction measured by visual analog scale (VAS).

Secondary outcomes included the number of responders (patients with at least 30% pain reduction) and pain threshold to pressure measured by algometry. Three calibrated reviewers independently extracted data and assessed risk of bias, with disagreements resolved by discussion or a fourth reviewer. The authors used GRADE methodology to assess the quality of evidence.

The 13 included RCTs comprised 656 total participants: 366 in BoTN-A intervention groups and 290 in placebo (saline) control groups. Study sizes ranged from 6 to 145 participants. The meta-analysis revealed that at 4 to 6 weeks, there was no significant improvement in pain intensity in the BoTN-A group compared with placebo (standardized difference in means [SDM], –0.110; 95% confidence interval [CI], –0.344 to 0.124; P = .356). However, at 2 to 6 months, there was a significant improvement in pain intensity in the BoTN-A group compared with placebo (SDM, –0.360; 95% CI, –0.623 to –0.096; P = .008).

The number of study participants who responded to treatment (at least 30% pain reduction) was not statistically significantly different between groups (risk ratio, 1.346; 95% CI, 0.922-1.964; P = .123). Pain threshold to pressure measured by algometry at approximately 2 months also showed no significant difference between groups (SDM, 0.131; 95% CI, –0.178 to 0.440; P = .405). In a subgroup analysis of studies injecting only muscles of mastication (masseter and temporalis), pain at 1 to 2 months significantly improved with BoTN-A (SDM, –0.494; 95% CI, –0.882 to –0.106; P = .013). No major adverse events were reported in any of the included studies.

Minor adverse events were transient and included flu-like symptoms, headache, increased muscle pain post-injection, difficulty smiling, and muscle weakness. According to GRADE, the quality of evidence was moderate for pain intensity outcomes and low for secondary outcomes due to risk of bias, small number of pooled studies, and small sample sizes.

This systematic review and meta-analysis provides moderate-quality evidence that BoTN-A injections can significantly reduce pain in patients with head and neck chronic myofascial pain syndrome, but this benefit emerges at 2 to 6 months rather than in the first 4 to 6 weeks. The delayed onset of significant pain relief suggests that BoTN-A's mechanism may involve more than just muscle paralysis, possibly including inhibition of pain mediators. For clinicians, this means patients should be counseled that improvement may take several months to become apparent. The lack of significant difference in responder rates and pressure pain thresholds indicates that BoTN-A may not work for all patients or may not improve all aspects of MPS.

The absence of major adverse events supports the safety of this treatment, though minor transient effects are common. However, the authors note important limitations: inconsistency in dosages (ranging from 10 to 50 units per trigger point), injection sites, and follow-up periods across studies. The overall risk of bias in included studies was unclear to high, and sample sizes were generally small. The authors recommend additional larger studies with standardized methodology, consistent dosing, and longer follow-up periods to confirm these results.

They also suggest future research compare BoTN-A with other treatments like anesthetic trigger point injections, physical therapy, and pain medications, and investigate whether BoTN-A is best reserved for refractory cases or can be used earlier in treatment. Economic considerations are also relevant, as BoTN-A is costly, used off-label for MPS, and may require repeated injections every 3 months.