. 2024 May 20;86(7):4112–4122. doi: 10.1097/MS9.0000000000002183

Table 1.

Main characteristics of the selected studies.

References	Diagnostic criteria and muscles involved	Study design	Number of patients	Mean age (±SD)/age range	Follow-up protocol	Intervention (I)	Control (C)	Outcome variables	Outcome	Adverse effect
Von Lindern et al. ³⁴	Chronic facial pain Masseter, temporal and medial pterygoid	RCT	I: 60 C: 30	NR	Baseline, 4w	BTX-A: 35 U in each side of the muscle	0.9% saline solution	Pain (VAS 0–10)	Patients who received botulinum toxin improved by a significant mean reduction on subjective pain scores and there was a significant difference compared with the placebo group	Side effects in the form of swallowing difficulty or temporary paralysis of a muscle of facial expression occurred in only 1 patient and they were completely reversible after 4w
Guarda-Nardini et al. ³³	RDC/TMD Masseter and temporal	RCT	I: 10 C: 10	25–45	Baseline, 1 w, 4w, 12w	BTX-A: 30 U in each masseter muscle and 20 U in each anterior temporal muscle	0.9% saline solution	Pain at rest and at chewing (VAS 0–10); Mastication efficiency (VAS 0–10); MMO (mm); Protrusive and laterotrusive movements (mm); Functional limitation during usual jaw movements (0–4); Subjective efficacy of the treatment (0–4); Tolerance of the treatment (0–4)	Patients treated with BTX-A had a higher subjective improvement in their perception of treatment efficacy than the placebo subjects	NR
Kurtoglu et al. ³²	RDC/TMD Masseter and temporal	RCT	I: 12 C: 12	I: 29.6±12.7 (16–53) C: 23.4±4.7 (20–34)	Baseline, 2w, 4w	BTX-A: 30 U in each masseter muscle and 20 U in each anterior temporal muscle	0.9% saline solution	EMG (mV); Bio-behavioral questionnaire (pain and psychological status)	Comparisons of pain, disability, and psychological status showed no statistical difference over time for the placebo or study groups	No side effects were evident
Ernberg et al. ³¹	RDC/TMD Masseter	RCT	I: 12 C: 9	26–50	Baseline, 4w, 12w	BTX-A: 50 U in each masseter muscle	0.9% saline solution	Pain (VAS 0–100); Physical and emotional function; Global improvement; MMO; PPT and PPTol	No significant differences in pain reduction were found between BTX-A injection and saline injection in patients with persistent myofascial pain	Side effects reported by the patients the first week after injections were frequent and of varying intensity but unrelated to the drug. All side effects had resolved at the 1-month follow-up
Guarda-Nardini et al. ³⁰	RDC/TMD Masseter and temporal	RCT	I: 15 C: 15	I: 47.7±14.3 C: 43.2±13.9	Baseline, 1h, 12w	BTX-A: 150 U for each side	Fascial manipulation	Pain (VAS 0–10); MMO	Both treatment protocols provided significant improvement over time for pain symptoms. The two treatments seem to be almost equally effective, fascial manipulation being slightly superior to reduce subjective pain perception, and botulinum toxin injections being slightly superior to increase jaw range of motion
De Carli et al. ²⁹	Myofascial pain Masseter and temporal	RCT	I: 7 C: 8	Mean: 38	1d, 3d, 5d, 8d, 10d, 12d, 15d, 30d	BTX-A: 60 U in each masseter muscle and 30 U in each anterior temporal muscle; 15d later, 30 U in each masseter muscle and 15 U in each anterior temporal muscle	Low-level laser	Pain (VAS 0–10); MMO	Both therapies were effective in reducing pain, but the effect of low-level lasers was faster than the use of BTX-A. Both treatments showed no statistically significant improvement in mouth opening	NR
Gupta et al. ³⁶	TMD Masseter and temporal	RCT	I: 12 C: 12	20–50	Baseline, 2w, 4w	BTX-A: 30 U in each masseter muscle and 20 U in each anterior temporal muscle	isotonic saline solution	EMG; Behavior questionnaire scores (pain and psychological status)	The behavioral questionnaire results for the study group showed a statistically significant relief from the pain. Whereas in control group, no statistically significant reduction in the pain and improvement in the daily life activities was found	No signs of any kind of adverse reaction were noted except local needle site reactions such as redness
Jadhao et al. ³⁵	Bruxism and myofascial pain Masseter and temporal	RCT	I: 8 C1: 8 C2: 8	20–35	Baseline, 1w,12w, 24w	BTX-A: 30 U in each masseter muscle and 20 U in each anterior temporal muscle	C1: isotonic saline solution C2: no injections	Pain at rest and at chewing (VAS 0–5); Maximum bite force	BTX-A is effective for treatment of bruxism to reduce myofacial pain and the occlusal force compared with the placebo group	NR
Patel et al. ²⁸	TMD Masseter, temporalis and pterygoid	RCT	I: 10 C: 9	NR	Baseline, 4w	IncobotulinumtoxinA: 50 U into each masseter, 25 U into each temporalis, and 10 U into each external pterygoid muscle	0.9% saline solution	Pain (VAS 0–10); Pain medication usage; Masticatory muscle tenderness	We demonstrate the utility of IncobotulinumtoxinA injection in the treatment of TMD refractory to pain medication and other conventional treatments in comparison to placebo	Patients noted no adverse events during the study
Kütük et al. ²⁷	Myofascial pain Lateral pterygoid	RCT	I: 20 C: 20	I: 33.0±6.8 C: 34.6±9.3 (21–54)	Baseline, 6w	BTX-A: 25 U at each tigger point, 25–150 U in total	Dry needling	Pain (VAS 0–10); MMO; functional limitation (0–3); jaw strength (0–3); palpable muscular spasms (0–4)	Pain relief at rest was more effective with the use of the dry needling technique after 6w. Both treatments produced significant pain relief and improved function in patients with myofascial pain	NR
Yurttutan et al. ²⁶	RDC/TMD Masseter and temporal	RCT	I: 24 C: 25	I: 30.5±9.95 C: 31±7.33	Baseline, 24w	BTX-A: 30 U in each masseter muscle and 15 U in each anterior temporal muscle	Occlusal splint	Pain (VAS 0–10); JFLS-8; OBC-21	Both the use of an occlusal splint and BTX injection will benefit TMD patients, and BTX therapy was more effective than the occlusal splint therapy	None of the patients reported any adverse effects related to the BTX injections or occlusal splint therapy during or after the treatment period
De La Torre Canales et al. ²⁵	RDC/TMD Masseter and temporal	RCT	I1: 20 I2: 20 I3: 20 C1: 20 C2: 20	36.8± 5.6	Baseline, 1w, 2w, 3w, 4w, 12w, 24w	I1: BTX-A low (10 U in each temporalis and 30 U in each masseter) I2: BTX-A medium (20 U in each temporalis and 50 U in each masseter) I3: BTX-A high (25 U in each temporalis and 75 U in each masseter)	C1: 0.9% saline solution (0.4 ml in temporalis and 0.6 ml in masseter) C2: OA	Pain (VAS 0–10); PPT; EMG, Masticatory Performance, Muscle thickness, CBCT	Compared to the placebo, subjective pain of BTX-A groups was significantly lower after 14 days and up to the end of the study; however, compared with OA, no statistical differences were found. Regardless of the dose, BoNT-A was as effective as OA on MFP	A transient decline in masticatory performance and muscle contraction, and a decrease in muscle thickness and coronoid and condylar process bone volume were found as dose-related adverse effects of BoNT-A
Montes-Carmona et al. ²⁴	RDC/TMD and DC/TMD Masseter, temporal and lateral pterygoid	RCT	I: 20 C1: 20 C2: 20	I: 42.40±5.19 C1: 42.95±7.01 C2: 45.40±6.76	Baseline, 1w, 2w, 4w, 8w, 12w, 24w	BTX-A: 12 U in each masseter muscle, 12 U in each anterior temporal muscle, 4 U in lateral pterygoid muscle, and 4 U in medial pterygoid muscle	C1: 0.9% saline solution C2: 2% lidocaine with vasoconstrictor: 0.6 ml in each masseter muscle, 0.6 ml in each anterior temporal muscle, 0.2 ml in lateral pterygoid muscle and 0.2 ml in medial pterygoid muscle	Pain (VAS 0–10); parameters of jaw range (MMO, protrusion, right and left laterotrusion); TMJ affectation questionnaires	BTX-A significantly reduced pain compared to saline and lidocaine. The effects lasted up to 6 months and were more intense in patients with localized myofascial pain than in patients with referred remote pain	No significant adverse reactions were observed
De La Torre Canales et al. ²³	RDC/TMD Masseter and temporal	RCT	I: 18 C1: 18 C2: 18	I: 34.6±6.5 C1: 30.8±6.9 C2: 30.3±6.9	Baseline, 4w	BTX-A: 30 U in each masseter and 10 U in each anterior temporal muscle	C1: 0.9% saline solution C2: acupuncture	Pain (VAS 0–100), PPT, EMG	After 1 month of follow-up, all therapies reduced the self-perceived pain in patients with MFP. BTX-A was not superior to acupuncture in pain reduction, but both were superior to SS; moreover, BTX-A was the only treatment able to improve PPT values	Only patients treated with BTX-A reduced the EMG activity in the injected muscles which should be considered as an adverse effect. Besides, patients receiving BTX-A injections also reported adverse effects like edema and pain during injection, being the last also reported by the SS group
Kaya et al. ²²	Bruxism and myofascial pain Masseter and temporal	RCT	I: 20 C: 20	Mean: 26.333 (18–45)	Baseline, 2w, 6w, 12w, 24w	BTX-A: 24 U in each side of the masseter muscle	Occlusal splint	Pain (VAS 0–10); maximum bite force	Low dose BTX-A and occlusal splint use were effective in eliminating bruxism-related pain but not superior to each other.	NR
De La Torre Canales et al. ²¹	RDC/TMD and DC/TMD Masseter and temporal	RCT	I1: 20 I2: 20 I3: 20 C: 20	18–45	Baseline, 4w, 24w	I1: BTX-A low (10 U in each temporalis and 30 U in each masseter) I2: BTX-A medium (20 U in each temporalis and 50 U in each masseter) I3: BTX-A high (25 U in each temporalis and 75 U in each masseter)	0.9% saline solution	Mandibular motion (pain-free opening, maximum unassisted and assisted opening, and right and left lateral movements), Muscle pain while palpation (0–3)	BTX-A, independent of dosage, improves mandibular range of motion and muscle pain to palpation of the masseter and temporal muscles in persistent MFP patients compared with saline injections	NR
Rady et al. ²⁰. 2022	DC/TMD Lateral Pterygoid Muscle	RCT	I: 9 C1: 9 C2:9	I: 23.22±2.1 C1: 24.22±2.9 C2: 23.22±2.1	Baseline, 12w	BTX-A: 30 U in the lateral pterygoid muscle	C1: ARA C2: LLLT	Pain (VAS 0–10), articular disc position, joint space index, time of recovery	BTX-A and LLLT could be considered effective alternative treatment modalities to ARA regarding reducing joint pain, clicking, and improving disc position in patients with symptomatic DDwR	Patients receiving BTX-A showed diminished contra-lateral mandibular movements after injection, with no other side effects noted
Rezazadeh et al. ¹⁹	RDC/TMD Lateral Pterygoid Muscle	RCT	I: 18 C: 18	I: 28.28±7.9 C: 24.78±4.5	Baseline, 1w, 4w, 12w	BTX-A: 15 U in the lateral pterygoid muscle	Saline solution	Pain (VAS), jaw movements (MMO, lateral and protrusion movement), click severity, Helkimo index	Click and VAS decreased after BTX injection, but the difference was not statistically significant compared to the control group	NR
Ayala et al. ¹⁸	DC/TMD Masseter	RCT	I: 7 C: 7	Mean 29.7±5.4	Baseline, 4w	BTX-A: 30 U in the masseter	Saline solution	Pain (VAS), condyle-fossa relationship	Both BTX-A and saline injections produced a significant decrease in VAS scores, but there were no significant differences between the two groups	NR
Gonzalez-Perez et al. ¹⁷	DC/TMD Masseter, temporal and lateral pterygoid	RCT	I: 26 C: 26	I: 39.11±9 C: 41.96±9.88	Baseline, 4w, 8w, 12w	BTX-A: 16 U in each masseter muscle, 16 U in each anterior temporal muscle and 16 U in each lateral pterygoid muscle	PNE	Pain at rest and during chewing (VAS 0–10); mouth opening, lateral movements, protrusion; TMJ involvement (0–100); TMJ impairment (0–100)	Both BTA and PNE showed high efficacy and safety in reducing pain and improving muscle function for the treatment of chronic masticatory myalgia. This improvement was sustained over a 3-month period in both groups	No side effects were detected with BTA, while four cases of self-limited pain and bruising at the puncture site were reported in the PNE group

ARA, anterior repositioning appliance; BTX-A, botulinum toxin type A; C, control group; CBCT, cone beam computed tomography; d, days; DC/TMD, diagnostic criteria for temporomandibular disorders; DDwR, disc displacement with reduction; EMG, electromyography; h, hours; I, intervention group; JFLS-8, jaw function limitation scale; LLLT, low-level laser therapy; m, months; MFP, myofascial pain; MMO, maximum mouth opening; NR, not reported; OA, oral appliance; OBC-21, Oral Behavior Checklist; PNE, percutaneous needle electrolysis; PPT, pressure pain threshold; PPTol, pressure pain tolerance; RCT, randomized controlled trial; RDC/TMD, research diagnostic criteria for temporomandibular disorders; VAS, visual analog scale; w, weeks.