Table 1.
Extracted study characteristics of the 40 included RCTs
| Authors, year | Study design | Subgroup diagnosis | Criteria used | Age of patients (years) | Male:female ratio | Treatment groups (no. of participants) | Duration of treatments/frequency | Outcomes measure | Follow-up time | Risk of bias |
|---|---|---|---|---|---|---|---|---|---|---|
| Alencar et al. (2014) [56] | RCT | Myofascial jaw pain | AAOP |
G1: 37 G2: 36.5 G3: 36.9 |
G1: 1:15 G2: 0:15 G3: 1:15 |
G1: placebo (15) G2: cyclobenzaprine (15) G3: tizanidine (15) |
G1: every day for 3 weeks G2: every day for 3 weeks G3: every day for 3 weeks |
Pain VAS | 3 weeks | Low |
| Bhalla et al. (2019) [57] | RCT | Myofascial pain | Clinical examination |
G4: NM G5: NM G6: NM |
G4: NM G5: NM G6: NM |
G4: ibuprofen + chlorzoxazone or carbamazepinen (10) G5: ibuprofen + chlorzoxazone or carbamazepine + holistic treatment (10) G6: holistic treatment (10) |
G4: every day for 2 weeks G5: every day for 2 weeks, including 60 min of holistic treatment the first day G6: 60 min of holistic treatment the first day |
Pain VAS | 3 months | High |
| Cahlin et al. (2011) [58] | RCT | Osteoarthritis | RDC/TMD |
G1: 54 G7: 61 |
G1: 1:10 G7: 1:6 |
G1: placebo (29) G7: glucosamine sulphate (30) |
G1: every day for 6 weeks G7: every day for 6 weeks |
Pain VAS MMO |
6 weeks | Low |
| Christidis et al. (2015) [59] | RCT | Myofascial pain | DC/TMD |
G1: 39.1 G8: 38.3 |
G1: 1:10 G8: 1:10 |
G1: placebo (20) G8: granisetron (20) |
G1: once a week for 3 weeks G8: once a week for 3 weeks |
Pain VAS MMO |
6 months | Low |
| Cigerim and Kaplan (2020) [60] | RCT | Myofascial pain | DC/TMD |
G1: 27.0 G9: 27.0 G10: 27.0 G11: 27.0 |
G1: 1:4 G9: 1:4 G10: 1:4 G11: 1:4 |
G1: placebo/control = paracetamol (47) G9: naproxen (42) G10: naproxen + codeine (40) G11: naproxen + single-dose dexamethasone (40) |
G1: every day for 1 week G9: every day for 1 week G10: every day for 1 week G11: every day for 1 week |
Pain VAS | 4 weeks | Low |
| Cömert Kiliç (2016) [61] | RCT | Osteoarthritis | DC/TMD |
G12: 32 G13: 28 |
G12: 1:8 G13: 1:3 |
G12: arthrocentesis + PRP injections (18) G13: arthrocentesis plus HA injection (13) |
G12: arthrocentesis + 1 mL PRP injection initially, and then four consecutive 1 mL PRP injection in TMJ at monthly intervals G13: arthrocentesis + a single intraarticular injection of HA |
Pain VAS |
G12:11.6 months G13: 12.8 months |
Some concerns |
| Da Silva Ramalho et al. (2023) [62] | RCT | Myofascial pain | Not specified |
G14: 39 G15: 37 |
G14: 1:4 G15: 1:4 |
G14: BTX-A in masseter (10) G15: BTX-A in masseter and temporalis (10) |
G14: single-session BTX-A injection in masseter, bilaterally (1 mL into every facial point, three points in each muscle) G15: single-session BTX-A injection in masseter and temporal muscles (1 mL into every facial point, three points in each masseter and two points in each temporal muscle) |
Pain VAS | 6 months | Some concerns |
| De la Torre Canales et al. (2021) [64] | RCT | Myofascial pain | RDC/TMD |
G1: 31 G16: 30 G17: 35 |
0:54 |
G1: placebo (n = 18) G16: acupuncture (n = 18) G17: BTX-A low (n = 18) |
G1: single-session bilateral injection in masseter and anterior temporalis NaCl 0.9% was bilaterally injected into the same muscles and sit G16: four sessions of traditional acupuncture, one 20-min session/week for 1 month G17: single-session bilateral injection in masseter and anterior temporalis using 30 U and 10 U of BoNT-A, distributed in five sites/muscles |
Pain VAS | 1 month | Low |
| De la Torre Canales et al. (2021) [65] | RCT | Myofascial pain | RDC/TMD |
G1: 37 G17: 37 G18: 37 G19: 37 G20: 37 |
0:100 |
G1: placebo G18: OA (n = 20) G17: BTX-A low (n = 20) G19: BTX-A medium (n = 20) G20: BTX-A high (n = 20) |
G1: single-session saline (0.9%) intramuscular injection (0.4 mL in m temporalis and 0.6 mL in masseter) G18: OA every night for 6 months G17: single-session intramuscular injection BTX-A low 10 U in m temporalis and 30 U in masseter G19: single-session intramuscular injection BTX-A medium 20 U in m temporalis and 50 U in masseter G20: single-session intramuscular injection BTX-A high 25 U in m temoralis and 75 U in masseter |
Pain VAS | 6 months | Low |
| De la Torre Canales et al. (2022) [63] | RCT | Myofascial pain | RDC/TMD | – | – |
G17: BTX-A-low (n = MD) G19: BTX-A-medium (n = MD) G20: BTX-A-high (n = MD) |
G17: BTX-A-low (masseter 30 U, temporalis 10 U), G19: BTX-A-medium (temporalis 20 U, masseter 50 U) G20: BTX-A-high temporalis 25 U, masseter 75 U) |
Pain VAS | 6 years | Some concerns |
| De la Torre Canales et al. (2022) [66] | RCT | Myofascial pain | RDC/TMD |
G1: 18–45 G17: 18–45 G19: 18–45 G20: 18–45 |
0:80 |
G1: placebo (n = 20) G17: BTX-A low (n = 20) G19: BTX-A medium (n = 20) G20: BTX-A high (n = 20) |
G1: saline solution 0.9%. 1–4: bilateral injection G17: 10 U in each temporalis and 30 U in each masseter G19: 20 U in each temporalis and 50 U in each masseter G20: 25 U in each temporalis and 75 U in each masseter |
Pain VAS MMO |
6 months | Low |
| Ernberg et al. (2011) [67] | RCT | Myofascial pain | RDC/TMD |
G1: 38 G14: 38 |
G1: 1:10 G14: 1:10 |
G1: placebo (n = 21) G14: BTX-A intramuscular (masseter) (n = 21) |
G1: single-session intramuscular isotonic saline masseter injection G14: single-session intramuscular BTX-a (50 U) injection |
Pain VAS MMO |
7 months | Low |
| Gencer et al. (2014) [68] | RCT | Internal derangement of the TMJ |
Wilke’s classification G1: Control groups selected from early-stage (I) patients G21–G23: Late-intermediate (IV) and late-stage (V) patients included in the study groups |
G1 40 G21: 36 G22: 38 G23: 40 |
G1: 12/13 G21: 11/14 G22: 11/14 G23:11/14 |
G1: intraarticular injection saline solution (n = 25) G21: HA intraarticular injection (n = 25) G22: betamethasone intraarticular injection (n = 25) G23: tenoxicam intraarticular injection (n = 25) |
G1 intraarticular injection saline solution G21: HA G22: betamethasone G23: tenoxicam |
Pain VAS | 6 weeks | Low |
| Guarda-Nardini et al. (2008) [69] | RCT | Myofascial pain | RDC/TMD |
G1: 25–45 G24: 25–45 |
1:1 |
G1: placebo (n = 10) G24: BTX-A (n = 10) |
G1: single-session intramuscular injection G24: single-session with 4 BTX-A intramuscular injections (masseter 30 U, temporalis anterior 20 U) |
Pain VAS MMO |
6 months | Some concerns |
| Guarda-Nardini et al. (2012) [70] | RCT | Myofascial pain | RDC/TMD | G25: 48 G26: 43 | 1:3 |
G25: BTX-A masseter and temporalis muscle (n = 15) G26: three sessions with fascial manipulation treatment (n = 15) |
G25: single session of multiple botulin toxin injections in the temporalis and masseter muscles (150 U) G26: 3× (±1) 50-min sessions on a weekly basis, for a total of 150 (±50) min over a 2–4-week span |
Pain VAS MMO |
3 months | Some concerns |
| Haghighat et al. (2013) [71] | RCT | Symptomatic osteoarthrosis | RDC/TMD |
G27: 27 G28: 27 |
1:3 1:3 |
G27: ibuprofen 400 mg (n = 30) G28: glucosamine sulphate 1500 mg (n = 30). |
G27: twice a day for 3 months G28: once a day for 3 months |
Pain VAS MMO |
3 months | High |
| Herman et al. (2002) [72] | RCT | Myofascial pain | RDC/TMD |
G1: 30 G29: 27 G30: 24 |
G1: 1:2 G29: 1:5 G30:: 1:8 |
G1: placebo (n = 15) G29: clonazepam (n = 13) G30: cyclobenzaprine (n = 13) |
G1: placebo capsule G29: capsule 1 h before bedtime for 3 weeks G30: capsule 1 h before bedtime for 3 weeks |
Pain VAS | 3 weeks | High |
| Isacsson et al. (2019) [73] | RCT | Unilateral TMJ arthralgia | DC/TMD |
G1: 56 G31: 48 |
G1: 1:3 G31: 1:6 |
G1: placebo (n = 27) G31: methylprednisolone (n = 27) |
G1: single-session intraarticular injection G31: single-session intraarticular injection |
Pain VAS MMO |
6 weeks | Low |
| Jayachandran et al. (2017) [74] | RCT | TMJ osteoarthritis | Clinical examination |
G32: 49 G33: 49 G34: 49 |
G32: 13:17 G33: 13:17 G34: 13:17 |
G32: diclofenac sodium 50 mg (n = 10) G33: diclofenac sodium + oral enzymes [bromelain, trypsin, rutoside trihydrate] (n = 10) G34: oral enzyme ([romelain, trypsin, rutoside trihydrate] (n = 10) |
G32: twice a day for 10 days G33: twice a day for 10 days G34: twice a day for 10 days |
Pain VAS | 10 days | High |
| Kang et al. (2018) [75] | RCT | Myalgia | DC/TMD |
G1: M: 30, F: 29 G35: M: 30, F: 29 G36: M: 30, F: 29 G37: M: 30, F: 29 G38: M: 30, F: 29 |
G1: 6:5 G35: 8:5 G36: 5:6 G37: 6:5 G38: 2:3 |
G1: saline in masseter (n = 11) G35: morphine 1.5 mg in masseter (n = 13) G36: morphine 5 mg masseter (n = 11) G37: lidocaine masseter (n = 11) G38: morphine 5 mg trapezius (n = 5) |
G1: single bolus intramuscular injection G35: single bolus intramuscular injection G36: single bolus intramuscular injection G37: single bolus intramuscular injection G38: single bolus intramuscular injection |
Pain VAS | 48 h | Low |
| Khalighi et al. (2016) [76] | RCT | Myofascial pain | RDC/TMD |
G39: 36 G40: 36 |
1:3 |
G39: naproxen 500 mg + placebo laser sessions (n = 20) G40: active laser (diode 810 nm CW) as treatment + placebo drug (n = 20) |
G39: naproxen daily for 3 weeks + 12 placebo laser sessions G40: 12 active low-level laser sessions + daily placebo drug for 3 weeks |
Pain VAS MMO |
2 months | Low |
| Kopp et al. (1985) [76] | RCT | Arthralgia | Clinical examination |
G1: 46 G41: 46 |
G1: 1:7 G41: 1:7 |
G1: intraarticular injection of 0.5 mL sodium hyaluronate (10 mg/mL) (n = 18) G41: intraarticular injection of 0.5 mL of corticosteroid betamethasone (n = 15) |
G1: single intraarticular injection G41: single intraarticular injection |
Helkimos index | 4 weeks | Low |
| Louw et al. (2019) [78] | RCT | TMJ arthralgia | RDC/TMD |
G42: 44 G43: 50 |
G42: 1:3 G43: 1:23 |
G42: intraarticular injections 20% dextrose + 0.2% lidocaine (n = 30) G43: intraarticular injections 0.2% lidocaine (n = 24) |
G42: intraarticular injections at 0, 1, and 2 months G43: 0.2% lidocaine; intraarticular injections at 0, 1, and 2 months At 3-month follow-up, allocation groups were revealed; participants in both groups were offered open-label injection of 20% dextrose/0.2% lidocaine monthly on a by-request basis |
Pain VAS MMO |
1 year | Low |
| Marini et al. (2012) [79] | RCT | TMJ osteoarthritis or arthralgia | RDC/TMD |
G44: 14–54 G45: 14–54 |
G44: 1:2 G45: 1:2 |
G44: palmitoylethanolamide (n = 12) G45: ibuprofen (n = 12) |
G44: palmitoylethanolamide 300 mg (morning) + 600 mg (evening) for 7 days and then 300 mg twice a day for an additional 7 days G45: ibuprofen 600 mg |
Pain VAS MMO |
2 weeks | Low |
| Mejersjö and Wenneberg (2008) [80] | RCT | TMJ osteoarthritis | RDC/TMD |
G18 : 62 G32: 62 |
G18: 1:14 G32: 1:14 |
G18: OA (n = 15) G32: diclofenac 50 mg (n = 14) |
G18: OA every night for 3 months G32: 2–3 times a day for 3 months |
Pain VAS MMO |
1 year | Some concerns |
| Montes-Carmona et al. (2020) [81] | RCT | Localized myalgia, myofascial pain, referred pain | DC/TMD | G1: 43 G37: 45 G46: 42 |
G1: 6:1 G37: 4:1 G46: 4:1 |
G1: placebo (n = 20) G37: lidocaine (n = 20) G46: BTX-A (n = 20) |
G1: single-session injection of 0.9% saline solution in masseter and temporalis mucles G37: single-session injection of 2% lidocaine with vasoconstrictor in masseter and temporalis mucles G46: single-session injection of onabotulinumtoxin A |
Pain VAS MMO |
6 months | Some concerns |
| Mustafa et al. (2018) [82] | RCT | TMJ hypermobility | Patient history and clinical examination |
G47: 25 G48: 24 G49: 27 G50: 25 |
G47: 4:5 G48: 1:2 G49: 1:8 G50: 1:2 |
G47: saline solution + lidocaine (n = 9) G48: 10% dextrose (n = 10) G49: 20% dextrose (n = 9) G50: 30% dextrose (n = 9) |
G47: injections into four different areas of each TMJ in four sessions at monthly intervals G48: injections into four different areas of each TMJ in four sessions at monthly intervals G49: injections into four different areas of each TMJ in four sessions at monthly intervals G50: injections into four different areas of each TMJ in four sessions at monthly intervals |
Pain VAS MMO |
4 months | Some concerns |
| Nitecka-Buchta et al. (2018) [83] | RCT | Myalgia | DC/TMD |
G1: 40 G51: 37 G52: 43 |
G1: 7:8 G51: 1:2 G52: 5:8 |
G1: placebo/saline (n = 15) G51: collagen injections (MD Muscle [Guna]) (n = 15) G52: 2% lidocaine without a vasoconstrictor injection (n = 13) |
G1: masseter triggerpoint injections at day 0 and day 7 G51: masseter triggerpoint injections at day 0 and day 7 G52: masseter triggerpoint injections at day 0 and day 7 |
Pain VAS MMO |
14 days | Some concerns |
| Priyadarshini et al. (2021) [84] | RCT | TMJ internal derangement | Wilkes stages II or III |
G18: 28 G53: 32 |
G18: 1:2 G53: 1:2 |
G18: OA (n = 17) G53: prolotherapy 50% dextrose (n = 17) |
G18: 12 hours/day for 3 months G53: four sessions of intraarticular injection: day 1, day 14, day 42, and day 82 |
Pain VAS MMO |
1 year | Some concerns |
| Refahee et al. (2022) [85] | RCT | Myofascial pain | DC/TMD |
G1: 31 G54: 36 |
G1: 1:5 G54: 1:5 |
G1: saline master trigger point injection (n = 90) G54: MgSo4 masseter trigger point injection (n = 90) |
G1: single intramuscular injection G54: single intramuscular injection |
Pain VAS MMO |
6 months | Low |
| Refai et al. (2011) [86] | RCT | Painful TMJ subluxation or dislocation | Patient history and clinical examination |
G55: 30 G56: 23 |
G55: 1:2 G56: 0:6 |
G55: saline solution + 2% mepivacaine (n = 6) G56: dextrose 10% + 2% mepivacaine (n = 6) |
G55: four intraarticular injections each 6 weeks apart G56: four intraarticular injections each 6 weeks apart |
MMO | 8 months | Some concerns |
| Rezazadeh et al. (2022) [87] | RCT | Painful TMJ clicking and tender lateral pterygoid muscle | RDC/TMD |
G1: 25 G57: 28 |
G1, G57: 17:19 |
G1: placebo/saline (n = 18) G57: BTX-A 300 U (n = 18) |
G1: single-session intramuscular injection m pterygoidies lateralis G57: single-session intramuscular injection m pterygoidies lateralis |
MMO Helkimos index |
3 months | Low |
| Sakalys et al. (2020) [88] | RCT | Masseter myofascial pain | Simons D, Travell J, Simons L. Travell and Simons’ Myofascial Pain | G43: 47 G58: 49 |
G43: 3:22 G58: 6:19 |
G43: lidocaine masseter injection (n = 25) G58: PRP injection (n = 25) |
G43: single-session intramuscular injection m masseter G58: single-session intramuscular injection m masseter |
Pain VAS | 4 weeks | Low |
| Sousa et al. (2020) [89] | RCT | Arthralgia | DC/TMD |
G18: 41 G59: 41 G60: 37 G61: 37 |
G18: 1:4 G59: 1:4 G60: 1:4 G61: 1:4 |
G18: OA (n = 20) G59: OA + intraarticular betamethasone (n = 20) G60: OA + intraarticular sodium hyaluronate (n = 20) G61: OA + intraarticular PRP (n = 20) |
G18: OA every night for 6 months G59: OA every night for 6 months + single-session intraarticular injection G60: OA every night for 6 months + single-session intraarticular injection G61: OA every night for 6 months + single-session intraarticular injection |
Pain VAS MMO |
6 months | Low |
| Tchivileva et al. (2020) [90] | RCT | Myalgia | DC/TMD |
G1: 34 G62: 34 |
G1: 1:4 G62: 1:2 |
G1: placebo (n = 99) G62: extended-release propranolol hydrochloride [60 mg, twice a day] (n = 100) |
G1: Twice a day for 10 weeks G62: Twice a day for 10 weeks |
MMO | 10 weeks | Low |
| Thie et al. (2001) [91] | RCT | Osteoarthritis | Confirmed on computed tomography |
G27: 39 G28: 37 |
G27: 1:8 G28: 1:8 |
G27: ibuprofen (n = 28) G28: glucosamine sulphate (n = 21) |
G27: once a day for 90 days G28: once a day for 90 days |
MMO | 90 days | Low |
| Tjakkes et al. (2007) [92] | RCT | Arthralgia, osteoarthrosis, and osteoarthritis | RDC/TMD |
G1: 33 G63: 33 |
G1: 1:18 G63: 1:18 |
G1: placebo (n = 19) G63: ultracain (n = 19) |
G1: single-session intraarticular injection G63: single-session intraarticular injection |
Pain VAS | 3 weeks | Low |
| Vidor et al. (2013) [93] | RCT | Myofascial pain | RDC/TMD |
G1: 30 G64: 32 |
G1: 0:32 G64: 0:32 |
G1: placebo (n = 16) G64: melatonin (n = 16) |
G1: at bedtime for 28 days G64: at bedtime for 28 days |
Pain VAS | 28 days | Low |
| Winocur et al. (2000) [94] | RCT | Unilateral TMJ pain | Patient history and clinical examination |
G1: 38 G65: 36 |
G1: 1:3 G65: 1:5 |
G1: Placebo (n = 13) G65: 0.025% capcacin cream (n = 17) |
G1: vehicle cream applied to the painful area four times/day G65: capcacin cream applied to the painful area four times/day |
MMO | 4 weeks | Low |
| Zarate et al. (2020) [95] | RCT | Arthralgia | RDC/TMD |
G42: 45 G43: 50 |
G42: 1:5 G43: 1:5 |
G42: dextrose prolotherapy (20% dextrose/0.2% lidocaine) G43: 0.2% lidocaine (n = 15) |
G42: intraarticular injection at 0, 1, and 2 months (n = 14) G43: intraarticular injection at 0, 1, and 2 months (n = 15) |
MMO | 3 months | Low |
G1: placebo, G2: cyclobenzaprine, G3: tizanidine, G4: ibuprofen + chlorzoxazone or carbamazepine, G5: ibuprofen + chlorzoxazone or carbamazepine + holistic treatment, G6: holistic treatment, G7: glucosamine sulfate, G8: granisetron, G9: naproxen, G10: naproxen + codeine, G11: naproxen + single-dose dexamethasone, G12 arthrocentesis + PRP injections, G13: arthrocentesis plus HA injection, G14: BTX-A in masseter, G15: BTX-A in masseter and temporalis, G16: acupuncture, G17: BTX-A Low, G18: OA, G19: BTX-A medium, G20: BTX-A high, G21: HA intraarticular injection, G22: betamethasone intraarticular injection, G23: tenoxicam intraarticular injection, G24: Botox in masseter and temporalis, G25: BTX-A injections in masseter and temporalis muscle, G26: three sessions with fascial manipulation treatment, G27: ibuprofen, G28: glucosamine, G29: clonazepam, G30: cyclobenzaprine, G31: intraarticular injection of methylprednisolone, G32: diclofenac sodium, G33: diclofenac sodium + oral enzymes (bromelain, trypsin, rutoside trihydrate), G34: oral enzyme (bromelain, trypsin, rutoside trihydrate), G35: morphine 1.5 mg masseter, G36: morphine 5 mg masseter, G37: lidocaine masseter, G38: morphine 5 mg trapezius, G39: naproxen + 12 placebo laser sessions, G40: low-level laser treatment + placebo drug, G41: intraarticular injection corticosteroid betamethasone, G42: intraarticular injections 20% dextrose + 0.2% lidocaine, G43: intraarticular injections 0.2% lidocaine, G46: BTX-A, G47: intraarticular injection saline solution + lidocaine, G48: intraarticular injection 10% dextrose, G49: intraarticular injection 20% dextrose, G50: intraarticular injection 30% dextrose, G51: collagen muscle injections, G52: 2% lidocaine without vasoconstrictor muscle injections, G53 intraarticular injection 50% dextrose, G54: magnesium sulfate masseter trigger point injection, G55: intraarticular saline + 2% mepivacaine, G56: intraarticular dextrose 10% + 2% mepivacaine, G57: BTX-A single-session intramuscular (m pterygoideus lateralis) injection, G58: PRP intramuscular injection, G59: OA + intraarticular betamethasone, G60: OA + intraarticular sodium hyaluronate, G61: OA + intraarticular PRP, G62: extended-release propranolol hydrochloride, G63: intraarticular ultracain, G64: melatonin, G65: 0.025% capcacin cream
AAOP American Academy of Orofacial Pain, BTX-A botulinum toxin-A, CW continuous wave, DC/TMD diagnostic criteria for temporomandibular disorders, HA hyaluronic acid, MgSo4 magnesium sulfate, MD missing data, DMMO maximal mouth opening, NM not mentioned, OA occlusal appliance, PRP platelet-rich plasma, RCT randomized controlled trial, RDC/TMD Research Diagnostic Criteria for Temporomandibular Disorders, TMJ temporomandibular joint, VAS visual analogue scale