Table 2.
(a) Quantitative findings regarding the effect of BoNT-A treatment on muscle pain intensity, (b) Quantitative findings regarding the effect of BoNT-A treatment on mandibular movements, (c) Quantitative findings regarding the effect of BoNT-A treatment on adverse events
| Outcome Intervention(s) | Author, year | Number of studies/number of participants | Results / findings | Heterogeneity |
|---|---|---|---|---|
| (a) | ||||
| Pain intensity in jaw muscles | Ahmed, 2019 | Not reported | Negligible effect favors BoNT-A [SMD -0.19 (95% CI -0.35, 0.03), p<0.05] | Moderate (I2 = 32%, p=0.16) |
|
Pain intensity BoNT-A vs. active placebo (saline), 0–3 wk Pain intensity BoNT-A vs. passive placebo (not penetrating skin), 0–3 wk Pain intensity BoNT-A vs. active placebo (saline), 1–6 mo Pain intensity BoNT-A vs. passive placebo (not penetrating skin) 1–6 mo PPT BoNT-A vs. active placebo, 1–3 mo |
Al-Moraissi, 2020 |
3/60 1/16 6/138 1/16 1/21 |
Very low-quality evidence [MD = 0.21 (95% CI -2.53, 2.95), NS] Very low-quality evidence [MD = 0.85 (95% CI -1.89, 3.59), NS] Low quality evidence [(MD -0.46 (95% CI -1.06, 0.15), NS] Low quality evidence [(MD -0.28 (95% CI -1.02, 0.46), NS] Very low-quality evidence [MD = 0.04 (−1.54, 0.57), NS] |
No statistically significant inconsistencies, no publication bias |
|
Pain intensity BoNT-A vs. placebo, overall Pain intensity BoNT-A vs. placebo, 0–5 mo Pain intensity BoNT-A vs. placebo, ≥6 mo PPT BoNT-A vs. placebo, overall |
Al-Moraissi, 2021 |
7/157 7/157 2/44 2/50 |
Very low-quality evidence [MD = -0.72 (95% CI -1.25, -0.19), p?] Very low-quality evidence [MD = -0.93 (95% CI -1.55, -0.31), p?] Very low-quality evidence [MD = -0.74 (95% CI -1.47, -0.02), p?] Very low-quality evidence [MD = -0.11 (95% CI -0.63, 0.40), NS] |
No statistically significant inconsistencies, no publication bias |
| Pain intensity BoNT-A vs. dry needling | Arribas-Pascual, 2023 | 4/Not reported | 1 SR showed better results of dry needling than wet needling (BoNT-A and other agents) | N/A (MA not possible) |
|
Pain intensity BoNT-A vs. saline Pain intensity BoNT-A vs. other treatment |
Awan, 2019 |
5/Not reported 2/Not reported |
2 of the studies reported improvements; No significant difference |
N/A (MA not possible) |
| Pain intensity BoNT-A vs. ctr or before-after | De la Torre Canales, 2017 | 3/152 | Reduced pain in all studies* | N/A |
| Pain intensity BoNT-A vs. ctr or before-after | De la Torre Canales, 2019 | 7/246 | Improved pain in all studies | N/A |
| Pain intensity | Delcanho, 2022 | 9/315 | 5 studies showed improved pain | N/A |
| Orofacial pain and muscular diseases | Di Francesco, 2022 | 11/527 | Varying results. No consensus could be reached on the therapeutic benefits of BoNT-A on TMDs | N/A |
| Pain | Griswold, 2023 | 2/85 | Similar short- and medium-term outcomes between BoNT-A and dry needling | N/A |
|
Pain reduction BoNT-A vs. saline 1–1.5 mo Pain reduction BoNT-A vs. saline in in masseter and temporalis only Pain reduction BoNT-A vs. saline 2–6 mo 30% pain reduction BoNT-A vs. saline |
Khalife, 2016 |
8/343 (3 TMD) 4/80 (3 TMD) 6/269 (3 TMD) |
No difference [SMD = -0.110; (95% CI -0.344, 0.1), p = 0.356] Significant difference [SDM = -0.494 (95% CI -0.882, -0.106), p = 0.13] Significant difference [SDM = -0.360 (95% CI -0.623, –0.096), p = 0.008] Significant difference [RR = 1.346 (95% CI 0.922, 1 964), p = 0.123] |
I2 = 26%, p = 0.221 Not reported I2 = 2%, p = 0.402 I2 = 0%, p = 0.983 |
|
Pain reduction BoNT-A vs. placebo (saline) Pain reduction BoNT-A vs. other treatment |
Machado, 2018 |
5/170 3/90 |
Positive effect on pain by BoNT-A in 2 studies, no effect 3 studies No difference between BoNT-A and other treatments |
N/A (MA not possible) |
|
Pain reduction BoNT-A vs. saline 1 mo Pain reduction BoNT-A vs. saline 3 mo Pain reduction BoNT-A vs. saline 6 mo Pain reduction BoNT-A vs. no treatment 3 mo Pain reduction BoNT-A vs. no treatment 6 mo Pain reduction BoNT-A vs. fascial manipulation 3 mo Pain reduction BoNT-A vs. LLLT 1 mo Pain intensity BoNT-A vs. conventional treatment 2 mo Pain intensity BoNT-A vs. conventional treatment 6 mo Pain intensity BoNT-A vs. conventional treatment 12 mo |
Machado, 2020 |
3/50 2/37 2/36 1/16 1/16 1/30 1/15 1/50 1/50 1/50 |
Significant effect of BoNT-A [SMD -1.74 (-2.94, -0.54), p = 0.004], Low quality evidence No effect of BoNT-A [SMD -0.89 (-2.04, 0.26), p = 0.13], Low quality evidence No effect of BoNT-A BoNT-A [SMD -0.89 (-2.74, 0.07), p = 0.06], Low quality evidence Non-significant difference [MD = -1.60 (-4.30, 1.10), NS] Non-significant difference [MD = -1.80 (-3.67, 0.07), NS] Higher pain intensity BoNT-A after treatment [MD = 2.30 (0.80−3.80), clinically significant effect Non-significant difference [MD = 0.40 (2.53, 1.73), NS Significantly lower pain after BoNT-A [MD = 1.80 (2.10, 1.50) Significantly lower pain after BoNT-A [MD = 1.90 (2.25, 1.55) Significantly lower pain after BoNT-A [MD = 1.90 (2.25, 1.55) |
I2 = 0%, p = 0.38 I2 = 0%, p = 0.98 I2 = 51%, p = 0.15 N/A N/A N/A N/A N/A N/A N/A |
| Pain intensity BoNT-A vs. control | Ramos-Herreira, 2022 | 8/314 | Medium- to low-certainty evidence that low doses of BoNT-A are effective in the treatment of refractory TMD myofascial pain | N/A (MA not possible) |
| Pain intensity BoNT-A vs. placebo (saline solution) | Zhang, 2011 | 8/ | [SMD = -0.16 (95% CI -0.39, 0.06), p = 0.16] | I2 = 0%, p = 0.87 |
| (b) | ||||
| MMO BoNT-A vs. active placebo 1–6 mo | Al-Moraissi, 2020 | 3/81 | No difference [MD 1.31 (95% CI -1.40, 3.60), NS], Very low-quality evidence | No statistically significant inconsistencies, no publication bias |
| MMO BoNT-A vs. placebo overall | Al-Moraissi, 2021 | 3/71 | No difference [MD -0.04 (95% CI -0.65, 0.57), NS], Very low-quality evidence | No statistically significant inconsistencies, no publication bias |
| MMO BoNT-A vs. dry needling | Arribas-Pascual, 2023 | 4/Not reported | 1 SR showed better results dry needling than wet needling (BoNT-A and other agents) | N/A (MA not possible) |
| MMO BoNT-A vs. saline | Awan, 2019 | 5/Not reported | 2 of the studies reported improvement | N/A (MA not possible) |
| MMO BoNT-A vs. ctr or before-after | De la Torre Canales, 2019 | 7/246 | Improved mouth opening after BoNT-A in all studies | N/A |
| MMO BoNT-A vs. control | Delcanho, 2022 | 9/315 | 5 studies showed improved mouth opening | N/A |
|
MMO BoNT-A vs. saline MMO BoNT-A vs. control |
Machado 2018 |
3/56 2/45 |
No difference between BoNT-A and saline No difference between BoNT-A and fascial manipulation or LLLT |
N/A |
|
Mouth opening BoNT-A vs. saline 1 mo Mouth opening BoNT-A vs. saline 3 mo Mouth opening BoNT-A vs. saline 6 mo Mouth opening BoNT-A vs. fascial manipulation Mouth opening BoNT-A vs. LLLT 1 mo |
Machado, 2020 |
2/41 1/21 1/20 1/30 1/15 |
No difference [SMD = 2.05 (-2.80, 0.89), p = 0.41] No difference [SMD = -0.90 (-8.26, 6.46), p = 0.81] No difference [SMD = 4.99 (-2.47, 12.27), p = 0.19] No difference between groups No difference [MD = 0.30 mm (10.10, 10.79), NS] |
I2 = 0%, p = 0.85 N/A N/A N/A N/A |
| (c) | ||||
| Presence of AE | Awan, 2019 | 5/Not reported | Worsening of pain, dysphagia, discomfort chewing after BoNT-A | N/A (MA not possible) |
| Presence of AE | De la Torre Canales, 2019 | 7/246 |
The most common adverse effects were temporary regional weakness, tenderness over the injection sites, and minor discomfort during chewing. Three studies reported asymmetric smile. one study reported mild to severe adverse effects (reduction in the size of the masticatory muscle, paresthesia, eye drooping or muscle weakness, difficulty swallowing, speech changes, perioral swelling, and bruising. |
N/A |
| Presence of AE | Delcanho, 2022 | 9/315 | No significant adverse events | N/A |
| Presence of AE | Khalife, 2016 | No major adverse events. Transient and short-lasting minor adverse events occurred in both the treatment and the control groups | N/A | |
|
Any adverse events BoNT-A vs. placebo 1 mo Any adverse events BoNT-A vs. placebo 3 mo Adverse events BoNT-A vs. fascial manipulation Adverse events BoNT-A vs. conventional treatment |
Machado, 2020 |
7/207 4/141 1/30 1/50 |
No difference [SMD 1.34 (0.72, 2.50), p = 0.36], Low quality evidence No difference [SMD 1.17 (0.32, 4.28), p = 0.81], Low quality evidence No adverse events in any group No adverse events in any group |
I2 = 0%, p = 0.72 I2 = 44%, p = 0.18 N/A N/A |
|
Bone volume BoNT-A vs. ctr 3 and 6 mo Bone density BoNT-A vs. ctr Cortical thickness 3 and 12 mo |
Moussa, 2023 |
3/130 2/156 3/105 |
No difference [MD = −2.36% (−11.82, 7.09), p = 0.6] Non-significant decrease after BoNT-A [−4.43% (−9.15, 0.29) p = 0.06] Significant decrease after BoNT-A [MD = −6.34% (−10.25, −2.42), p = 0.001] |
I2 = 0%, H2 = 1 (p not reported) I2 = 59.8%, H2= 2.49 (p not reported) I2 = 0%, H2= 1 (p not reported) |
| Bony changes mandible | owen, 2022 | 7/320 | Decreased cortical thickness, volume or density in 5 studies - Very low-quality evidence in the RCT | N/A |
BoNT-A botulinum toxin type A, RCT randomized controlled study, SR systematic review, MA meta-analysis, TMD temporomandibular disorders, LLLT low-level laser therapy, SMD standard mean difference, MD mean difference, WMD weighted mean difference, MCID minimally clinically important difference, CI confidence interval, RR risk ratio, NNH number needed to harm, MMO maximal mouth opening, AE adverse event
* According to the article, all five studies reported pain. However, three measured pain, one morning stiffness, and the other only bruxism episodes