Effectiveness of clove oil as a topical anesthetic during inferior alveolar nerve block: A randomized, single-blinded, active-controlled clinical study

Introduction

Managing pain during dental procedures promotes positive behavior in pediatric patients, and builds trust between a child patient and a dentist. There are many factors of dental fear and anxiety, such as the presence of many caries, previous bad dental experiences, and social and cultural factors, such as parental dental anxiety [1, 2]. The administration of local anesthesia is the main factor of patients’ discomfort and anxiety, particularly when using inferior alveolar nerve block (IANB) [3]. Therefore, many methods are used to relieve pain of needle insertion, including vibration [4, 5], coldness at the injection site [6], distraction techniques [7, 8], and application of different topical anesthetic agents [9]. In pediatric dentistry, topical anesthesia is widely used before local anes­thesia administration. It is effective on surface tissues of 2-3 mm in depth, acting by signal transmission blockade in the sensory nerve fibers. Benzocaine is the most commonly used topical anesthetic agent [10]. However, the increasing number of adverse effects related to topical anesthetic agents’ application, especially in children, is the main reason to search for alternative substances [11, 12].
Using herbs to relieve dental pain has been a popular option for centuries due to their availability, reliable effectiveness, and safety without adverse effects found in chemicals. Many plants have analgesic and anesthetic properties, such as clove, turmeric, and betel leaves [13]. Clove is one of the most popular spices, and it is made from the flower bud of an evergreen tree of conical shape, with an average height of 8-12 meters. It is rich in phenolic compounds, and used for food flavoring and many therapeutic purposes [14, 15]. In addition, it is employed in toothache treatment due to its eugenol content [16-18].

Objectives

This study aimed to investigate the effectiveness of clove oil (Clove oil, TACT Co.) and 20% benzocaine gel in reducing pain during IANB in children aged 7-11 years. The null hypothesis was that no statistically significant difference would be found between the effectiveness of clove oil and benzocaine 20% gel in reducing pain during the administration of IANB.

Material and methods

Trial design, ethics, and recruitment

It was a single‐blinded, parallel‐group, randomized, active-controlled study with two arms. Ethical consent was obtained from the Ethical and Scientific Committee of Damascus University (approval number: N1770). This study was performed in full accordance with the Declaration of Helsinki 2013 [19] and the CONSORT statement [20]. Dental procedure was explained in detail, and written informed consent was obtained from patients’ legal guardians. Participation was optional and confidential, and participants’ legal guardians could withdraw their consent at any time. This study was performed between June 2022 and October 2022 at the Department of Pedia­tric Dentistry, Damascus University, Syria, and was registered in the ISRCTN registry (No.: ISRCTN10078508) on October 18, 2023.
Inclusion criteria: 1) healthy children according to child health questionnaire (CHQ) [20]; 2) those aged 7-11 years; 3) children with no previous dental experience with local anesthesia; 4) patients required non-urgent dental treatment with IANB; 5) children definitely positive or positive according to Frankl’s behavior rating scale [22].
Exclusion criteria: 1) patients allergic to any anesthetic agent used in the study; 2) those with fascial space infections and/or dental abscesses; 3) children with special healthcare needs; 4) cases with odontophobia, according to Corah’s dental anxiety scale (DAS) [23].
The CONSORT flow diagram is shown in Figure 1. Sixty-three children with non-urgent dental treatment derived from the group referred to the Department of Pediatric Dentistry, Damascus University, were screened for eligibility by an experienced pediatric dentist. Based on inclusion criteria, 60 children were enrolled in the study, and were randomly assigned into two groups based on the topical anesthetic agent used: group 1 – control group, 20% benzocaine gel (Benzotics oral gel, Domina Pharmaceuticals, Damascus, Syria) (n = 30); group 2 – Clove oil consisting of 83.7% eugenol (n = 30).

Sample size calculation

Sample size was calculated using G*Power version 3.1.9 software (Heinrich‐Hein‐Universität‐Düsseldorf, Germany; http://www.gpow-er.hhu.de/). In the power analysis conducted for non-parametric Mann-Whitney test, a large effect size (d = 0.80) was assumed. To achieve a power of 0.80 with an a level of 0.05, it was determined that a minimum of 27 subjects per group would be required to identify the expected difference between the two independent groups.

Randomization and blinding

Children were randomly assigned into two groups in a ratio of 1 : 1 using a simple randomization method. Patients were randomly allocated to each intervention arm with randomization online software: https://www.randomizer.org. The number of sets obtained was 2, with 30 participants per set. The range of numbers was from 1 to 60. It was a single-blinded study, where only one was blinded to which interventional arms children were assigned. Masking participants and the clinician was not possible due to the differences in physical pro­perties of the materials used.

Clinical procedure and primary outcome measures

Recruited children were randomly assigned into two groups. In the first group (control group), 20% benzocaine gel was applied, and in the second group, clove oil was used. Mucosa drying was done at the site of injection before application of the tested material, and then 0.3 ml of each topical anesthetic was applied using a Q-tip for three minutes [11]. IANB was performed by an experienced pediatric dentist to prevent inter-examiner variability. All participants were videotaped with a mobile device (Mi 9, Xiaomi) by a blinded outcome assessor, and data were stored as MP4 files protected by a password using third-party software. Injection was made more posteriorly and slightly lower, since in pediatric patients, the mandibular foramen is situated at a level lower. Therefore, the barrel of dental carpule syringe (Dental carpule syringe, Dental Laboratorio) was directed on the plane between two primary molars on the opposite side of the arch. A 27-gauge × 21 mm needle (Disposable dental needle, Shanghai Dochem Industries Co., Ltd., Shanghai, China), was inserted, and 1.8 ml of 2% lidocaine with epinephrine 1 : 80,000 (2% lidocaine HCL injection, Huons Co., Ltd., Seongnam, Korea) was injected [24]. Subsequently, a non-urgent dental treatment was performed. The dental carpule syringe was kept out of pediatric patient’s line of sight, and fearful words, such as “hurt”, “pain”, or “injection” were avoided during communication. Kappa coefficient of intra- examiner reliability was set at > 0.8. The following primary outcome measures were assessed:
1. Sounds, eyes, and motor (SEM) scale
SEM scale was employed to measure pain objectively during needle insertion, and it was evaluated by a blinded outcome assessor using the recorded videos. SEM scoring criteria were as follows:
Sound:
score 1 = comfort; no sound;
score 2 = mild discomfort; non-specific sound;
score 3 = moderate discomfort; louder sound, specific verbal complaints;
score 4 = severe discomfort; shouting, crying, and verbal complaints indicating severe pain.
Eye:
score 1 = comfort; no sign;
score 2 = mild discomfort; dilated eye without tears (anxiety sign);
score 3 = moderate discomfort; tears and sudden eye movements;
score 4 = severe discomfort; heavy crying.
Motor:
score 1 = comfort; relaxed body;
score 2 = mild discomfort; muscular contraction indicating pain;
score 3 = moderate discomfort; sudden and random movements of body and hand;
score 4 = severe discomfort; hand movements for defense, pulling head away [25].
2. Pain rating scale Wong–Baker faces pain rating scale (WBFPS) was used to subjectively assess pain. Children were requested by the clinicians to select a face that represented their pain level immediately after IANB administration. WBFPS six faces indications, with increasing degree of pain from left to right, were as follows:
face 0 = no hurt.
face 2 = hurts little bit.
face 4 = hurts little more.
face 6 = hurts even more.
face 8 = hurts whole lot.
face 10 = hurts worst [26].

Statistical analysis

Statistical analysis was performed with IBM SPSS software version 24 (IBM Corp., Armonk, NY, USA). Normality of data was verified using Kolmogorov-Smirnov test and Fischer’s exact test, while Mann-Whitney U test was applied to compare between study groups. Significance level was set at p < 0.05.

Results

Sixty children were included and randomly allocated into two groups. The demographic data of the partici­pants are presented in Table 1. More than half of the children (56.67%) were males, and the mean age was 8.18 years (standard deviation [SD]: 1.24; range, 7-11 years). No statistically significant difference was observed between the groups in baseline characteristics of the participants (p > 0.05), suggesting homogeneity of data. SEM and WBFPS were presented as mean, SD, standard error (SE), and maximum and minimum for each group (Tables 2 and 3). The mean score of SEM scale in the group 1 (1.10 ± 0.18) was approximately identical to that of the group 2 (1.06 ± 0.13). The mean score of WBFPS in the group 1 (1.03 ± 0.18) was comparable with that of the group 2 (0.93 ± 0.17), indicating that the physiological response to pain and the children’s subjective reporting of pain were at their minimum. The results of Mann-Whitney U test of SEM scale and WBFPS scores demonstrated no statistical difference between the two groups (p = 0.326 and p = 0.714, respectively) (Tables 2 and 3). These findings indicated that the results of the objective and subjective measurements of pain were comparable between the two groups.

Discussion

Dental fear and anxiety usually cause dental visit avoidance and poor oral hygiene [1]. There have been many recent developments in the field of local anesthesia, which can be used along with traditional techniques to reduce pain associated with needle insertion [4-8]. Topical anesthesia is considered the gold standard in pediatric dentistry, because of its safety and efficacy [11]. However, topical anesthetics have adverse effects [11, 12]. Therefore, this study aimed to investigate the effectiveness of clove oil and 20% benzocaine gel in reducing pain during IANB application in pediatric patients aged 7-11 years. Recently, there has been an increasing interest in the use of medicinal herbs in dental treatment and hygiene, especially in products, such as toothpastes. According to Janakiram et al. [27], non-herbal toothpastes are not superior to herbal toothpastes in controlling dental plaque due to their antimicrobial and astringent properties. Similarly, Shirakawa et al. [28] reported that toothpaste containing natural herbs reduces bacterial counts and improves periodontal status. In addition, according to Hashemi et al. [29], asafetida mouthwash was equally effective as chlorhexidine gluconate mouthwash in improving gingival health. Also, da Chuna et al. [30] suggested that Passiflora incarnata is an effective anxio­lytic before third molar surgical extraction compared with midazolam.
The current study included children aged 7-11 years, as children in this age group have improved cognitive ability and can report their pain intensity using appropriate pain scales [31, 32]. In this study, 20% benzocaine gel was applied because it is widely accepted among dentists and rapidly absorbed [11]. However, topical anesthetics have side effects, such as anaphylaxis, soft tissue swelling, and allergic effects. In addition, topical anesthetics are detected in plasma after intra-oral use, which is considered a source of concern. It causes systemic symptoms, including dizziness, chest pain, arrhythmia, and tachycardia. Moreover, large amounts of benzocaine can cause methemoglobinemia, a life-threatening condition that leads to unusual fatigue, nausea, vomiting, tachycardia, and dyspnea. Therefore, these side effects are the main reason for searching safer alternatives [33-37]. Clove oil is an essential oil extracted from the leaves of clove trees, and it is used in food, drinks, and toothpastes. Eugenol is the main component of the aromatic oil (70% to 90%) extracted from cloves [15]. According to Elbestawy et al. [38], clove essential oil has antibacterial and antibiofilm properties against resistant Helicobacter pylori strains. Furthermore, according to Kothiwale et al. [39], the regular use of clove mouth rinse has antiplaque and antigingivitic efficiency. This clove oil is an effective, safe, and inexpensive analgesic that is used to treat headache and toothache. The analgesic property is due to its ability to activate calcium and chloride channels, while the anesthetic property varies according to its concentration and duration of application. Clove oil has been suggested as an effective, safe, and natural topical anesthetic agent [13-16]. Therefore, it explains the use of clove oil as a topical anesthetic in the current study. Each material was applied for 3 minutes, because it is a widely accepted method to achieve adequate intensity and depth [11]. In the present study, self-report pain was evaluated using WBFPS visual scale, since it is quick and easy to use due to its minimal instruction [40]. SEM scale was employed for objective evaluation of pain during needle insertion, as many studies proved its reliability and ability to assess the relationship between pain and verbal and non-verbal behaviors [41].
The effectiveness of clove oil in reducing pain during IANB was comparable to that of 20% benzocaine gel. In addition, the physiological response to pain and the children’s subjective reporting of pain were at their mini­mum, indicating that both topical anesthetic are equally effective in controlling pain during IANB. This finding is consistent with a research of Alqareer et al. [42], who found that clove oil could replace benzocaine gel as a topical anesthetic before needle insertion into the buccal mucosa of the maxillary canine. Similarly, Anantharaj et al. [43] concluded that a clove-papaya-based topical gel containing 3% clove oil was as effective as benzocaine gel. Also, Havale et al. [44] found that clove oil can reduce pain sensation in children aged 6-10 years, and serve as an alternative to benzocaine gel. It is noteworthy that the application time of topical anesthetic in the studies by Anantharaj et al. [43] and Havale et al. [44] was only 1 minute, whereas it was 3 minutes in the current study. All these studies confirm the efficacy of clove oil as a cost-effective alternative to other topical anesthetics, especially considering its widespread use and availability in rural areas and low-income countries. Regarding the side effects of clove oil, Sarrami et al. [45] reported two cases of adverse local reactions, emphasizing that similar to other local anesthetics, caution should be exercised when using this substance.
The present study has some limitations. Blinding of children was not possible due to the differences in physi­cal state between benzocaine gel and clove oil, which led to the risk of bias. In addition, it was not possible to use a placebo as a negative control group due to ethical considerations.

Conclusions

Clove oil was as effective as 20% benzocaine gel in reducing pain during IANB. Furthermore, clove oil can be a non-expensive alternative in rural areas and low-income countries.

Disclosures

1. Institutional review board statement: The study was approved by the Ethical and Scientific Committee of Damascus University, approval number: N1770.
2. Assistance with the article: None.
3. Financial support and sponsorship: None.
4. Conflicts of interest: The authors declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article.

References