Comparative Analysis of the Effectiveness of the Topical Administration of Benzocaine and EMLA® on Oral Pain and Tactile Sensitivity

Objectives To compare the effectiveness of the topical administration of benzocaine and EMLA on oral pain and tactile sensitivity. Materials and Methods A randomized, double-blind, split-mouth clinical trial was carried out with 20 volunteers. The sensorial and quantitative tests were applied before the contact with topical anesthetic and after the application. Results In the superficial tactile perception test, when we compared each group singly, there were statistically significant values in the decrease of superficial tactile perception when compared to the moment prior to the application of anesthetic agents. For the sensitivity to mechanical pain, no statistical significant difference was observed at evaluated times. In the needle penetration test, in an intergroup analysis, we found a decrease in the pain sensitivity to needle penetration at 5 min (p=0.053) and at 10 min (p=0.019) after the contact of the anesthetic drug with the oral mucosa. Conclusion The application of topical anesthetic drugs reduces the discomfort associated with this procedure, mainly until the first 10 minutes. Only the needle penetration sensitivity test showed sufficient sensitivity to reveal a difference in the anesthetic effect between EMLA and benzocaine. This trial is registered with RBR-2N2GSW.


Introduction
Topical anesthesia is extremely important to a wide variety of dental procedures, such as periodontal probes, gingival manipulation, staple adaptation, preparation to in ltrative anesthesia, pediatric care, and traumatic lesions in the oral mucosa [1][2][3]. In this context, the main purpose of using topical anesthetic drugs is to reduce or relieve the painful stimulus caused by needle penetration, leading to signi cant control of pain and anxiety of the patient [1].
e ideal local anesthetic agent should be e ective even when administered topically. However, not all anesthetic bases present this characteristic [4]. In dentistry, benzocaine is one of the main commercially available topical anesthetic drugs. It is chemically classi ed as an amino ester and is available as a gel. Although this drug presents rapid onset of action, it has limited potency and short anesthetic duration, besides being exclusively used in mucous membranes [5].
EMLA (AstraZeneca do Brasil, Ltda., Cotia, SP, Brasil) is an anesthetic formulation de ned as an eutectic mixture of local anesthetic drugs composed of a combination of 2.5% prilocaine and 2.5% lidocaine. is formulation is indicated for pain control in several super cial cutaneous procedures [6,7]. Accordingly, in the oral cavity, satisfactory results have been evidenced in biopsies [8], periodontal probes [9], and prior to local anesthesia [10]. erefore, the aim of this study was to compare the e ectiveness of the topical administration of benzocaine and EMLA on oral pain and tactile sensitivity.

Materials and Methods
Twenty-four academics from the dentistry course of Dr. Leão Sampaio University Center were interviewed in this study. ree of these academics were excluded because they did not attend the second visit and another because of diabetes and incomplete medical records.
us, the study continued with 20 volunteers, including 12 women and 8 men with an average age of 22.8 years. e study was characterized as randomized, double-blind, split-mouth clinical trial.
e Research Ethics Committee of the Dr. Leão Sampaio University Center reviewed the procedures, including the recruitment and consenting process.
Healthy subjects (ASA I), meeting the criteria of the American Society of Anesthesiology (ASA) [11], were selected for this research, including nonpregnant, nonsmoker, nonnursing, with no history of allergies to local anesthetics, without chronic use of medications, with complete natural dentition and without reports of dysesthesia in the face or oral cavity. Participants who did not meet these criteria were excluded from the study.
Initially, we performed a molding of the maxillary arch of the participants, followed by the preparation of a model in plaster and acetate molding, with involvement of the teeth and palate. A relief area was created in wax and placed on the cast model on the palate, at 2 mm from the gingival margin, between the teeth 15 and 16 and 25 and 26, to create a reservoir for the local anesthetic drug ( Figure 1). e participants of this research were comfortably seated in the dental chair at 45°in relation to the ground, with the head resting on a at surface, in a silent room with temperature set at 23°C. ey were instructed to keep their eyes closed and concentrate on the examination.
We applied 0.4 g of 20% benzocaine (DFL Industria e Comércio SA, Rio de Janeiro, RJ, Brazil) to the reservoirs, and in the opposite portion, we deposited an equivalent quantity of EMLA (AstraZeneca do Brasil, Ltda., Cotia, SP, Brazil) ( Figure 2). e sides of deposition of the topical anesthetic were randomly selected, by sorting a sealed envelope. e mucosa was previously dried with gauze, and then the tray was positioned and maintained for 5 min. Subsequently, the excess anesthetic was removed from the teeth and gingiva, and the area was dried with air jets to prevent changes in sensitivity and/or sliding of the needle or laments, which could result in misinterpretations of the examinations.
An examiner who was not present in the previous period was responsible for assessing the values related to the pain stimulus, which consisted of three quantitative sensory methods: super cial tactile perception, sensitivity to mechanical pain, and sensitivity to needle penetration. e tests were applied at the same previously identi ed points, beginning from the patient's right side to the left and sequentially repeated for three times each test.

Super cial Tactile Perception.
is parameter was evaluated through the application of Semmes-Weinstein micro laments (Sorria-Bauru, Bauru/SP, Brazil), consisting of a set of 7 nylon laments with equal lengths, rounded tips, and di erent diameters and colors, which allows the application of forces of di erent intensities (0.05 to 300 g/mm 2 ) on a surface. e laments were vertically applied at the predetermined points, in ascending order of diameter, until perception and identi cation of the stimulus by the participant. e lament in which the stimulus was perceived was recorded. Of note, three measurements were taken for each side.

Sensitivity to Mechanical Pain.
e sensitivity to mechanical pain was determined through application of a constant force using the orange-colored Semmes-Weinstein lament (which corresponds to a force of 10 g/mm 2 ) in contact with the mucosa, for 2 seconds. e evaluated patient quanti ed the level of pain through the visual analogue scale (VAS) [12], which assigns a value of 0 for "complete absence of pain" and 10 for "the most intense possible pain level." ree measurements were made for each side.

Sensitivity to Needle Penetration.
A short 30G dental needle (DFL Industria e Comércio SA, Rio de Janeiro, RJ, Brazil) was vertically inserted at the points that had contact with the topical anesthetic drugs, at a depth of 2 mm, controlled by means of a rubber stopper. e evaluated patient quanti ed the level of pain through the visual analogue pain scale [12] as previously described. ree measurements were taken for each side. e measurements started before the tray was applied and after contact with the topical anesthetic drugs at 5, 10, 20, and 30 min.

Statistical Analysis
e data were examined and classi ed as nonparametric and nonnormal, after application of the D'Agostino's test, and median values were applied in the three evaluation methods. For intergroup analysis (Benzocaine x EMLA), the Wilcoxon test was applied. To perform comparisons in the same group, according to the time of contact with the topical anesthetic drug, the Friedman test was applied. All time points (5, 10, 20, and 30 min) were assessed, and odds below 0.05 were classi ed as statistically signi cant. All data were evaluated using the SPSS (SPSS, Windows version 19.0, SPSS Inc., USA).

Results
In the super cial tactile perception test, we observed a similar result between the side treated with EMLA and the side that was treated with benzocaine, represented by a decrease of tactile response to higher pressures in the oral mucosa in the ve minutes time point, obtained with the use of thicker Semmes-Weinstein laments ( Figure 3). However, when comparing both groups (EMLA versus benzocaine), no statistical repercussions were observed at the evaluated times (Table 1).
When we compare each group singly, we observed that, at the ve minutes point of measurement, there were statistically signi cant values in the decrease of super cial tactile perception when compared to the moment prior to the application of anesthetic agents. ese results were not statistically signi cant for the other times (10, 20, and 20 minutes) ( Table 2). e test of sensitivity to mechanical pain revealed that the patients presented minimal discomfort as attested by the analogue scale [12]. A comparative analysis between the treatments with the two drugs demonstrated a slight increase in the mechanical sensitivity in the benzocaine-treated side (Figure 4), at ve minutes point. However, no statistical signi cant di erence was observed at evaluated times, either in the intergroup analysis (Table 1) or in an isolated group assessment ( Table 2).
In the test of sensitivity to needle penetration, the benzocaine-treated side was more sensitive to the painful stimulus when compared to the EMLA-treated side, evidenced by higher visual analogue pain scores ( Figure 5). In an intergroup analysis, we found a decrease in the pain sensitivity to needle penetration at 5 min (p � 0.053) and 10 min (p � 0.019) after the contact of the anesthetic drug with the oral mucosa (Table 1), with statistical relevance. When we evaluated each group separately, we observed that the side in contact with benzocaine had a statistical difference in point time of 30 minutes (Table 2), when compared to the time prior to contact with the topical anesthetic. No other information with statistical relevance was observed for the other time evaluated and in the group treated with EMLA.   International Journal of Dentistry 3

Discussion
Dental anesthesia is among the main procedures associated with patient phobia in dental o ces, leading a considerable number of adults to avoid dental treatments because of the fear of anesthetic puncture [13]. Nevertheless, patients with anxiety due to aversion to dental procedures usually report greater pain sensation during anesthesia than those who do not fear the anesthetic act [14]. Topical anesthesia has a main objective to annul pain prior to anesthetic in ltration [15]. is procedure optimizes in ltrative local anesthesia by reducing the level of anxiety of the patient before needle penetration, as well as decreasing the number of perforations required and the amount of anesthetic administered [2].
With the exception of the needle penetration sensitivity test, the other instruments of evaluation were not sensitive enough to show a statistical di erence between EMLA and benzocaine, unlike other reports that revealed clearer results on the superiority of EMLA [10,16]. e statistically signi cant results in super cial tactile perception test, on both sides, when evaluated singly (Table 2), may re ect a blockade of Aβ bers and mechanoreceptors. Although it was not possible to measure the intensity of this blockade, previous studies have demonstrated that topical administration of 5% lidocaine interferes with the bers that are responsible for touch perception, which justi es the maintenance of touch sensitivity in some patients, even after contact with the topical anesthetic drug [17]. e in uence of anesthetic bases on nociceptors and C bers, both associated with pain stimuli, were evaluated by the tests of sensitivity to mechanical pain and needle penetration sensitivity. e rst test was not sensitive enough to con rm statistical di erences between EMLA and benzocaine in the two modalities of evaluation (intergroups and isolated). In our study, the VAS was used only to measure the intensity of pain. As observed in others reports [18]. if we had used it to quantify both degree of discomfort and pain, it might re ect more consistent values.
In line with other studies [16], in the needle penetration sensitivity test, the side in contact with EMLA revealed less pain stimulation ( Figure 5). When we correlated the repercussions of the anesthetic e ect over the evaluated times (5,10,20, and 30 min), statistically signi cant outcomes were obtained in the rst 5 minutes and 10 minutes after contact with the topical anesthetic, when the needle penetration sensitivity test was applied (Table 1). ese results support the evidence that local anesthetic drugs a ect more the pain threshold than the sensory threshold [19].
Although we did not perform an evaluation of the time of action of the evaluated anesthetics, the main results with statistical relevance were present in the rst 5 and 10 minutes of contact. is fact is corroborated by other studies that reveal duration of anesthetic e ect over 20 minutes for EMLA [18].
To achieve a consistent evaluation of the topical anesthetic action, the methods of measurement should include not only the response to pain through the visual analogue scale, but also the in uence on the somatosensory system, evaluated in this study by the super cial tactile perception and corroborated by other works that demonstrated favorable results for EMLA in the e ectiveness of changing sensory and pain thresholds [20].
us, the use of Semmes-Weinstein needles and laments in the measurement of the sensitive and painful responses in the present study were e ective and simple to acquire and apply. Accordingly, earlier reports rati ed the reliability and validation of these instruments for use in the oral cavity. However, electronic measurements have showed greater precision in the results [18,20].
In contrast to benzocaine, which has speci c characteristics for use in the mouth, the prilocaine/lidocaine combination (EMLA) used in this study has properties that impair its use in the oral mucosa. In fact, the unpleasant taste was one of the complaints of the participants, and the addition of avor would facilitate their acceptance, especially in pediatric dentistry. In addition, the low viscosity of this product makes di cult its administration on the palate, requiring the formulation of a tray with a speci c reservoir. Although better avored formulations containing lidocaine/prilocaine with speci c applicators are currently available, their use is restricted to periodontics and they have limited scope [9].
Reports of local or systemic adverse e ects of topical anesthetic drugs are uncommon [21] and were not evidenced in this study. e absorption and bioavailability of the drug depend on the contact surface, concentration, and time of application. erefore, the use of these drugs in integral surfaces, for a brief time and at a low dose, as used in this work, is relatively safe. Accordingly, in this study, we used only 1/4 (0.4 g) of the recommended maximum dose (2 g) of benzocaine and 1/10 of the dose that achieves plasma levels that are toxic to the central nervous system [22,23]. Finally, we conclude that the application of topical anesthetic drugs prior to anesthetic in ltration in the oral mucosa reduces the discomfort associated with this procedure, mainly until the rst 10 minutes. Only the needle penetration sensitivity test showed su cient sensitivity to reveal a di erence in the anesthetic e ect between EMLA and benzocaine. An improvement in the other two methods, associated with an increase in the number of participants, may provide a more complete analysis of the both topical anesthetics.