Table 1 Characteristics of included clinical trials investigating herbal extracts for orofacial pain treatment categorized by type of orofacial pain.

Periodontal Pain

18

Shahakbari et al., 2014

SBRCT

Pericoronitis

Camellia sinensis

Green tea Mouthwash

Clorhexidine

Each patient received a 250-ml dark bottle containing the mouthwash (green tea 5%) and was instructed to rinse with this mouthwash twice a day for 7 days.

23

Keceli et al., 2015

DBRCT

Free gingival graft

Glycyrrhiza glabra, Alpinia officinarum, Vitis vinifera,

Urtica dioica, Thymus vulgaris

topical Ankaferd Blood Stopper

Placebo

After removing the graft, wet gauze with the herbal extract was compressed to the donor site by the surgeon during 60 s with moderate finger pressure. six-month follow-up

33

Patil et al., 2018

RCT

Orthodontic pain

Atropa belladonna

Systemic Belladonna globules

Ibuprofen

In the Belladonna 6 C group, four globules given to patient. Patients were given two doses of medication of their respective groups, 1 h before placement of elastomeric separators which was administered in the department and one dose 6 h after the placement.

25

Das et al., 2019

TBRCT

Periodontal flap

Arnica montana, Calendula officinalis, Matricaria chamomilla, Hypericum perforatum, Aconitum napellus, Bellis perennis, Atropa Belladonna, Echinacea purpurea, Echinacea angustifolia, Hamamelis virginiana, Achillea millefolium, Symphytum officinale

Systemic Traumeel tablets

Ibuprofen

Ibuprofen, 600 mg and traumeel, 600 mg (up to three tablets) every 8 h for first 24 h and SOS (Si Opus Sit/if needed) thereafter for a period of 1 week as pain medication, respectively.

34

Anil et al., 2019

RCT

Periodontal flap

Curcuma longa

Topical Curcumin mucoadhesive film

Placebo

Curcumin mucoadhesive films of 0.5% were cut into smaller rectangular strips of 4–5 mm width and the length depending on the extent of flap surgery in each patient. UKirkland flap surgery was performed. After suturing, the preformed films were adapted on the gingiva in the test and control sites, respectively, over which periodontal pack (Coe-Pack) was placed

39

Alshibani et al., 2022

SBRCT

Periodontal Therapy

Zingiber officinale

Systemic Ginger tablets

Ibuprofen

ginger tablets (400 mg) every 12 h for 3 days and then as needed for pain

40

Al-Askar et al., 2022

SBRCT

Periodontal Therapy

Curcuma longa

Systemic Curcumin capsules

Mefenamic acid

Test group: patients received curcumin capsules (200 mg). The participants in the test and control groups were advised to orally take 1 MA tablet and 2 curcumin capsules, respectively, immediately after the procedure and then every 8 h for 3 days. After the third day, participants in the test and control groups were advised to take the respective analgesics as needed for pain.

Oral Surgery Pain

44

Alqareer et al., 2006

SBRCT

Anesthesia infiltration pain (pre-surgery)

Syzygium aromaticum

Topical Clove gel

1: Benzocaine

2: Placebo

home made clove gel. Approximately 2 g of material were applied to the buccal mucosa superior to the gingiva over the canine prominence, covering an area of about 1.5 cm in diameter for 4 min and then was reapplied for another minute. The material was reapplied because the authors were concerned about material washout by saliva.

21

Mohite et al., 2020

SBRCT

Anesthesia infiltration pain (pre-surgery)

Anacyclus pyrethrum, Spilanthes acmella

Topical herbal anesthesic in gel

Lignocaine

After isolation, the test region was dried by utilizing a sterile cotton gauze. The topical anesthetic to be tested was drawn for each participant and applied using a cotton applicator stick. After 10 min, a 26gauge sterile needle was inserted .

42

Jesudasan et al., 2015

DBRCT

Alveolar osteitis (post-surgery)

Syzygium aromaticum

Topical Eugenol paste

1: Chlorhexidine

2: No-treatment

After the third molar was extracted, eugenol-based paste was applied to the socket

41

Rayati et al., 2017

DBRCT

Extraction (surgery)

Zingiber officinale

Systemic ginger capsules

1: Ibuprofen

2: Placebo

one capsule of ginger containing 500 mg of ginger rhizome powder (Zintoma; Goldaru Co., Iran) All medications were administered orally and 6 hourly, 500 mg of ginger rhizome powder

43

Komasawa et al., 2018

SBRCT

Extraction (surgery)

Cinnamomi Cassiae, Syzygium aromaticum, Glycyrrhiza Uralensis, Ligusticum wallichii, Nuphar japonica, Quercus robur, Rheum rhabarbarum

Systemic Jidabokuippo granules

No-Treatment

Patients were given three oral doses (2.5 g each) of JDI (TJ-89, Tsumura Co, Tokyo, Japan) just before falling asleep the night before surgery, and in the morning and around noon on the day of surgery (total 7.5 g).

22

De Souza et al., 2021

TBRCT

Extraction (surgery)

Arnica montana, Calendula officinalis, Matricaria chamomilla, Hypericum perforatum, Aconitum napellus, Bellis perennis, Atropa Belladonna, Echinacea purpurea, Echinacea angustifolia, Hamamelis virginiana, Achillea millefolium, Symphytum officinale

Traumeel S intramuscular injection

Dexamethasone

Right after anesthezing an intramuscular injection in the masseter muscle of 2 mL at three different points

Oral Neuropathic Pain

45

Marino et al., 2010

DBRCT

Burning mouth syndrome

Capsicum annuum

Capsaicin mouthwash

1: Alpha-lipoic

2: Lysozymelactoperoxidase

3: Boric acid

daily oral rinses with capsaicin, 250 mg of red pepper emulsion in 50 ml of water for

24

Spanemberg et al., 2012

DBRCT

Burning mouth syndrome

Paullinia cupana, Trichilia catigua, Zingiber officinale, Ptychopetalum

olacoides

Systemic Catuama capsules

Magnesium silicate

take 2 capsules a day, before lunch and dinner, for 8 weeks after the first evaluation.

46

Pakfetrat et al., 2019

DBRCT

Burning mouth syndrome

Saffron

Systemic Crocin Tablets

Citalopram

For one group, citalopram (Sobhan Darou, Iran) was given orally once daily with an initial dose of 10 mg that increased to 20 mg after a week. For the other group, crocin tablets 15 mg (prepared by a pharmacologist) was prescribed twice daily. Both groups received the treatments for 11 weeks.

47

Bessho et al., 1998

RCT

Burning mouth syndrome

Bupleurum chinense, Pinellia ternata, Scutellaria baicalensis, Magnoliae Officinalis, Ziziphus mauritiana, Panax ginseng, Glycyrrhiza Glabra, Perilla frutescens, Zingiber officinale

Systemic Sai-boku-to Tablets

Diazepam + Vitamin B

Oral administration of 2.5 g of Sai-boku-to (TJ-96, Tsumura & Co, Tokyo, Japan) 3 times per day (before meals) for 3 months was prescribed.

48

Lee et al., 2007

DBRCT

Facial sensitivity and pain

Capsicum annuum

Topical Capsaicin cream

No-Treatment

Topical capsaicin cream (0·075%), which was applied to the mental area unilaterally, four times daily for 2 weeks. Around 40 µL of capsaicin cream (0·075%)* was applied topically four times daily for 2 weeks on a 4-cm2 area in the treatment side of the mental area. Subjects were instructed to squeeze a 6-mm long strip of capsaicin cream onto a cotton swab and vigorously apply it over the area

Endodontic Pain

49

Majji & Murthy, 2016

SBRCT

Dentinal hypersensitivity

Calendula officinalis, Plantago major

Calendula and plantago Toothpaste

1: Potassium nitrate

2: Calcium sodium phosphosilicate

3: Strontium chloride

Each patient was advised to brush their teeth in the usual manner for 3 min, twice daily, with soft bristle toothbrush, and to apply the dentifrice in an amount equal to about half the length of the bristle head.

20

Kar et al., 2019

DBRCT

Dentinal hypersensitivity

Spinacia oleracea, Syzygium aromaticum, Terminalia chebula, Terminalia bellirica, Phyllanthus emblica

Topical paste of palakya, lavanga, and triphala.

1: Potassium salt

2: Arginine

Desensitizing paste was applied over the isolated hypersensitive area. Using a disposable applicator tip, pea-sized amount of the toothpaste was applied over the isolated hypersensitive area of the tooth for 5 s, and a rotary polishing cup at moderate-to-high speed was used to polish the paste over this surface for 1 min.

Oral Mucosal Pain

17

Liu et al., 2022

DBRCT

Orthodontic wounds

Glycyrrhiza Glabra

Licorice mouthwash

Placebo

200 cc mouthwash bottle at the start of the study and after 2 days. The patients rinsed with the mouthwash for 10–20 s and four times daily.

50

Mansour et al., 2014

DBRCT

Aphthous ulcers

Commiphora myrrh

topical myrrh gel

Placebo

apply the drug to the ulcer four times a day (after meals and before bedtime) for 5 days using finger or cotton tip applicator and to refrain from eating and drinking for 30 min after application

28

Tadbir et al., 2015

DBRCT

Aphthous ulcers

Matricaria chamomilla

Topical chamomile application

1: Placebo

2: Triamcinolone

Chamomile in Orabase

51

Motallebnejad et al., 2008

DBRCT

Aphthous ulcers

Hypericum perforatum

Hypericum perforatum mouthwash

1: No-treatment

2: Placebo

topical hypericum containing mouthwash (0.5%) for seven days

26

Jiang et al., 2012

DBRCT

Aphthous ulcers

Allium sativum

Allicin Garlic oral adhesive tablets

Placebo

Subjects were instructed to apply 1 Allicin oral adhesive tablets 5 mg to the appointed ulcer 4 times a day (after meals and before bedtime) for 5 days (day 1 to day 5).

121

Deshmukh & Bagewadi, 2014

DBRCT

Aphthous ulcers

Curcuma longa

Topical Curenext gel

Triamcinolone

apply the gel three times a day on each ulcer after meals and not to consume food or water for half an hour after application. All patients were provided with same measuring applicator and were instructed about the quantity and method of gel application

52

Pourahmad et al., 2010

DBRCT

Aphthous ulcers

Vachellia erioloba

Camel thorn swish and swallow mouthwash

Placebo

(distillate) The patients were instructed to use 40 milliliters of the solution 4 times a day until they experienced complete resolution of their symptoms. The patients were instructed to keep the drug in their mouths for one minute and then swallow it. The camel thorn dose administered to patients was based on the normal dose used in Iranian folk medicine.

53

Babaee et al., 2012

DBRCT

Aphthous ulcers

Aloe vera

Topical Aloe vera gel

Placebo

To apply the gel on the lesions three-times a day by the patients for at

least ten days.

122

Kia et al., 2020a

DBRCT

Aphthous ulcers

Curcuma longa

topical Curcumin orabase paste

Triamcinolone

5% of Curcumin orabase apply the orabase three times a day after eating meals, for a 10-day period. The patients were asked to clean the lesion by soft and dry clean

gauze and then put 1 cm of the orabase on the wet tip of their fingers and dab it on the lesion with no rubbing action. Patients were advised to avoid eating and drinking for at least half an hour after drug application

123

Halim et al., 2013

SBRCT

Aphthous ulcers

Curcuma longa

Topical turmeric powder

Triamcinolone

apply the medication twice per day for 5 days

54

Yang et al., 2016

DBRCT

Aphthous ulcers

Taraxacum mongolicum, Isatis indigotica, Corydalis bungeana, Scutellaria baicalensis

Pudilan Keyanning toothpaste

Placebo

brush their teeth for 2–3 min, twice a day (in the morning and evening), each time covering two thirds the length of the toothbrush provided. After brushing the participants were asked to apply a little toothpaste to cover the ulcer surface with a cotton swab provided for 6 days

29

Ghalayani et al., 2013

DBRCT

Aphthous ulcers

Punica granatum

Topical Punica granatum gel

Placebo

apply the gel three times daily by placing a small sterile cotton pad impregnated with gel on the lesions for 1 min. They were asked not to eat for at least 30 min after administering the preparations.

55

Babaee et al., 2010

DBRCT

Aphthous ulcers

Myrtus communis

Topical Myrtle paste

Placebo

The paste was applied by subjects themselves four times a day for 6 days

30

Jin et al., 2017

RCT

Aphthous ulcers

Taraxacum mongolicum, Isatis indigotica, Corydalis bungeana, Scutellaria baicalensis

Systemic Pudilan oral solution

Placebo

Pudilan oral solution for 8 days at a dosage of 10 mL three times per day

124

Thomas et al., 2017

DBRCT

Oral lichen planus

Curcuma longa

Topical curcumin gel

Triamcinolone

Group 2 (curcumin oral gel thrice daily) and Group 3 (curcumin oral gel six times daily). Curenext Oral Gel (Piramel, Health Care, India) each gram of which contains curcuma longa extracts 10 mg having 1% Curcuminoids.

125

Kia et al., 2020b

DBRCT

Oral lichen planus

Curcuma longa

Systemic Nano-Curcumin capsule

Prednisolone

take one capsule of Nano-Curcumin 80 mg after having their breakfast

56

Jornet & Aznar-Cayuela, 2016

RCT

Oral lichen planus

Matricaria chamomilla

Topical Chamomile gel

Placebo

The patients received Topical Chamomile gel 2% together with instructions for their correct use. The preparations (0.5 mL/3 times a day) were applied uniformly to the oral cavity in the areas that presented symptoms, spreading the gel with the finger.

31

Keshari et al., 2015

RCT

Oral lichen planus

Curcuma longa

Topical curcumin ointment

Triamcinolone

Topical curcumin ointment (commercially available as Curenext Oral gel-Abbott Pharmaceuticals, India) each to be applied thrice daily for 2 weeks.

32

Chainani-Wu et al., 2012

RCT

Oral lichen planus

Curcuma longa

Systemic Curcumin C3 complex softgel

Placebo

6000 mg/d in 3 divided doses for 12 days

57

Mansourian et al., 2011

DBRCT

Oral lichen planus

Aloe vera

Aloe vera mouthwash

Triamcinolone

rinse the mouth with 2 tablespoons of AV mouthwash for 2 min, 4 times a day and expectorate.

58

Hasheminasab et al., 2020

DBRCT

Oral Mucositis

Plantago ovata

Plantago ovata mouthwash

1:Placebo

2: No-Treatment

The herbal compound consisted of a mixture of 500 mg of P. ovate husk in 30 mL water plus three drops of vinegar per dose, three times per day during their next chemotherapy cycle (cycle 1 of treatment)

63

Elhadad et al., 2020

SBRCT

Oral Mucositis

Matricaria chamomilla

Topical chamomile gel

Miconazol + Benzocaine

chamomile topical oral gel 3% alone which was prescribed three times daily, one day prior to the scheduled cycle of chemotherapy, lasting for 3 weeks

65

De Cássia Dias Viana Andrade et al., 2022

SBRCT

Oral Mucositis

Curcuma longa

Topical Curcumin photosensitizing agent

1: Photobiomodulation

2: Nystatin

The curcumin solution (10 mL) was sprayed inside the oral cavity remained for 10 min for impregnation with the mouth closed then the oral cavity was illuminated with a blue diode light emitter for 10 min. This was performed 1 time a week for 30 days, totalized 4 applications, during the period in which the patient was undergoing radiation and/or chemotherapy.

59

Aghamohammadi et al., 2018

DBRCT

Oral Mucositis

Zataria multiflora

Zataria Mouthwash

Placebo

Patients gargled the ZM mouthwash or a placebo before the beginning of the treatment three times daily and before each radiotherapy session.

60

Soltani et al., 2020

DBRCT

Oral Mucositis

Plantago major

oral consumption of plantago major syrup

Placebo

take plantago major L syrup 7.5 cc, three times a day for 7 weeks, from three days before the start of radiotherapy to the end of it. Patients were advised not to rinse their mouth for half an hour after taking the drug

61

Kia et al., 2021

DBRCT

Oral Mucositis

Curcuma longa

Systemic Curcumin Capsules

Placebo

The study group was received Curcumin nanomicelle capsules 80 mg twice a day and the control group took placebo two times a day for 7 weeks.

35

Patil et al., 2015

RCT

Oral Mucositis

Curcuma longa

Curcumin mouthwash

Clorhexidine

curcumin mouthrinse 0.004% to be used in 1:5 dilution for 1 min, three times daily for twenty days

36

Mansouri et al., 2016

RCT

Oral Mucositis

Aloe vera

Aloe vera mouthwash

Placebo

5 ml of aloe vera solution for two minutes three times a day for 14 days.

37

Hussain et al., 2019

RCT

Oral Mucositis

Nigella sativa

Nigella sativa oil Mouthwash

Nystatin + Tetracycline + Lidocaine + Dexamethasone

The patients in both groups received the NS oil mouth rinse and the magic mouthwash topically as a mouth rinse (10 ml each 6 h) daily, starting from the first day after the initiation of CT up to day 28 (the end of the CT).

62

Monsen et al., 2021

SBRCT

Oral Mucositis

Salvia officinalis

Salvia officinalis Mouthwash

Placebo

Salvia officinalis solution consisting of 2.5 g SO herbal tea/100 ml water. The SO herbal tea solution was based on dry extract of Salvia officinalis leaves from the Hospital Pharmacy (Sanivo Pharma AS), which were steeped for 2 min in boiled water. rinsing

with the assigned solution (10–15 ml) twice for 30s four times a day, and after each rinsing.

38

Wang et al., 2018

RCT

Oral Mucositis

Rheum rhabarbarum, Glycyrrhiza glabra, Mentha piperita, Scutellaria baicalensis, Liriope, Paeonia lactiflora, Scrophularia ningpoensis, Forsythia

Systemic Chining decoction

Epidermal growth factor

mixed with hot water, 200 mL daily, taken morning and evening, 100 mL each time, from the first day of radiotherapy until the completion of radiotherapy

64

Reis et al., 2016

SBRCT

Oral mucositis

Matricaria chamomilla

Chamomile infusion Cryotherapy

Cryotherapy

Patients in the chamomile group received a cup of ice chips made with chamomile infusion at 2.5%. Patients were instructed to swish the ice around in their oral cavity for atleast 30 min, starting 5 min before the chemotherapy infusion.

19

Najafi et al., 2017

DBRCT

Oral Mucositis

Glycyrrhiza Glabra

Glycyrrhiza mouthwash

Placebo

Glycyrrhiza or placebo were given to patients and they were asked to use 20 cc twice per day for 14 days after starting radiotherapy

66

Piyush et al., 2018

DBRCT

Oral submucous fibrosis

Curcuma longa

Systemic Curcumin tablet

Placebo

Curcumin tablet (300 mg) twice daily or Lycopene capsules (8 mg) twice daily for six months

126

Jiang et al., 2013

RCT

Oral submucous fibrosis

Salvia Miltiorrhiza

Salvianolic acid B Intralesional injection

Triamcinolone

All patients received an intralesional injection after 5 min of local anesthetic cream application (20% Topcaine; Medental, Balama City, USA) at weekly intervals for 20 weeks. Salvianolic acid B (4 mg).

27

Yadav et al., 2014

RCT

Oral submucous fibrosis

Curcuma longa

Systemic Turmix tablets

Dexamethasone + Hialuronic Acid + Lignocaine

oral administration of 2 tablets of Turmix given once daily for a period of 3 months

67

Hazarey et al., 2015

RCT

Oral submucous fibrosis

Curcuma longa

Longvida Curcumin tablets

Clobethasol

Longvida lozenges (Mfg Lic.: GA/1482) (400 mg lozenges) manufactured by Pharmanza Herbal Pvt. Ltd. The total daily dose decided was 2 g of Longvida lozenges.

68

Srivastava et al., 2021

RCT

Oral submucous fibrosis

Curcuma longa, Syzygium aromaticum

Systemic TurmNova lozenges and Clove oil

Dexamethasone

Patients were administered curcumin lozenges (TurmNova^®, Gelnova Laboratories Pvt. Ltd, Navi Mumbai, India) containing turmeric extract 100 mg along with clove oil 10 mg three times daily for 3 months. Patients were advised to chew these lozenges slowly followed by swallowing

Temporomandibular Disorder Pain

71

Chaimano et al., 2021

DBRCT

Temporomandibular disorder

Zingiber cassumunar, Curcuma longa, Cinnamomum camphora

Thai herbal compress ball

Placebo

The compress balls are applied on the painful muscle at least once a day. Two compress balls should be steamed in a stacked electric steamer pot for twenty minutes. After that, the first warm ball (approx 40ºC) was applied to the jaw muscle, then replaced with the second one when it was slightly lukewarm. The two herbal balls were alternately steamed and alternately used for twenty minutes. After each application, the balls were wrapped in a plastic bag and kept in the freezer until they could be reused. This study employed the reuse of herbal balls daily for one month

69

Li et al., 2009

DBRCT

Temporomandibular disorder

Mentha piperita, Cinnamomum camphora, Gaultheria fragrantissima, Santalum album, Eucalyptus

Topical Ping On ointment

Placebo

rub the ointment over the painful area and then to massage in a circular motion for 5 min twice a day. The area of application was just on the skin around the TMJ and affected muscles, which were usually the temporalis and masseters.

72

Nitecka-Buchta et al., 2019

DBRCT

Temporomandibular disorder

Cannabis

Topical CBD oil

Placebo

Oleum CBD 2.0 g (20% CBD oil). Group1 received CBD formulation. topical use to be applied on the skin surface of the masseter muscle, at the right and left side. Each patient had been taught on the procedure to apply the formulation in equal amounts (the size of peas) on both sides. Patients were informed that the formulation should be applied and rubbed gently into the skin surface (approximately 4 × 4 cm) and were supposed to apply it twice a day for up to a period of 14 days before the follow-up visit.

70

Campbell et al., 2016

DBRCT

Temporomandibular disorder

Capsicum annuum

Topical Capsaicin cream

Placebo

Topical capsaicin cream (8%), The investigator spread a 0.1-mL dollop of cream to a standardized area overlying the affected TMJ and superficial masseter and then covered the site with a cotton gauge for 2 h. This area extended 3 cm anteriorly and inferiorly from the posterior aspect of the TMJ. A square 3 × 3-cm template was cut into a rubber dental dam to standardize the application site. The drug was applied to the right or left side randomly for subjects without TMD, whereas for the TMD sufferers, the side that was reported as more painful was studied.