Efficacy and Safety of Botulinum Toxin Type A on Persistent Myofascial Pain: A Randomized Clinical Trial

Abstract

This study assessed the safety and efficacy of three different doses of BoNT-A for persistent myofascial pain (MFP). One hundred female subjects were randomly assigned into five groups (n = 20): oral appliance (OA), saline solution (SS) and three BoNT-A groups with different doses. Pain intensity and pressure pain threshold were evaluated up to 24 weeks after treatment. Adverse effects related to muscle contraction, masticatory performance, muscle thickness and mandibular bone volume were also assessed. Changes over time were compared within and between groups. The "nparLD" package and Wilcoxon signed-rank test were used to analyze the data. BoNT-A reduced pain intensity (p < 0.0001) and increased pressure pain threshold (p < 0.0001) for up to 24 weeks compared to the placebo. No differences were found between BoNT-A and OA at the last follow-up. A transient decline in masticatory performance (p < 0.05) and muscle contraction (p < 0.0001), and a decrease in muscle thickness (p < 0.05) and coronoid and condylar process bone volume (p < 0.05) were found as dose-related adverse effects of BoNT-A. Regardless of the dose, BoNT-A was as effective as OA on MFP. Notwithstanding, due to BoNT-A dose-related adverse effects, we suggest the use of low doses of BoNT-A in MFP patients that do not benefit from conservative treatments.

Keywords: bone loss; botulinum toxin type A; chronic pain; myofascial pain; temporomandibular disorders.

Figure 1

CONSORT diagram for participant enrollment.

Figure 2

Botulinum toxin effects on subjective pain intensity and in pressure pain threshold versus saline solution and oral appliance over time. OA: oral appliance; SS: saline solution; BoNTA: botulinum toxin type A; L: low; M: medium; H: high. (A) Mean; *** = p < 0.001 vs. saline solution; ** = p < 0.01 vs. saline solution; * p < 0.05; (B) Mean; *** = p < 0.001 vs. saline solution; ** = p < 0.01 vs. saline solution; * = p < 0.05; Mean; +++ = p < 0.001 vs. oral appliance; ++ = p < 0.01 vs. oral appliance; group: p = 0.023, time: p ≤ 0.0001, group x time: p ≤ 0.0001.

Figure 3

Clinical improvement (30%) in subjective pain.

Figure 4

Changes in root mean square scores (RMS µV) of maximum volunteer contraction (MVC) of botulinum toxin compared with saline solution and oral appliance over time. OA: oral appliance; SS: saline solution; BoNTA: botulinum toxin type A; L: low; M: medium; H: high; mean; *** = p < 0.001 vs. saline solution; ** = p < 0.01 vs. saline solution; +++ = p < 0.001 vs. oral appliance; ++ = p < 0.01 vs. oral appliance; ### = p < 0.001; group: p = 0.025, time: p ≤ 0.0001, group x time: p ≤ 0.0001.

Figure 5

Study flow diagram. RDC/TMD: Research Diagnostic Criteria for Temporomandibular Disorders; VAS: visual analogue scale; PPT: pressure pain threshold; EMG: electromyography; MP: masticatory performance; UI: ultrasound imaging; CBCT: cone beam computed tomography; CSL: counseling; OA: oral appliance; BoNT-A; botulinum toxin type A; SS: saline solution D: day.