|Year : 2020 | Volume
| Issue : 2 | Page : 177-183
Comparative evaluation of a novel herbal anesthetic gel and 2% lignocaine gel as an intraoral topical anesthetic agent in children: Bilateral split-mouth, single-blind, crossover in vivo study
Vedangi Arvind Mohite1, Sudhindra Baliga1, Nilima Thosar1, Nilesh Rathi1, Pramod Khobragade2, Rashi Srivastava1
1 Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Medical Sciences (Deemed to be University), Wardha, Maharashtra, India
2 Department of Pharmacology and Materia Medica, Datta Meghe Institute of Ayurvedic Medical College, Hospital and Research Centre, Nagpur, Maharashtra, India
|Date of Submission||15-May-2020|
|Date of Acceptance||15-May-2020|
|Date of Web Publication||28-Jun-2020|
Dr. Vedangi Arvind Mohite
Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha - 442 001, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Topical anesthetics have an intrinsic part to reduce pricking pain sensation due to needle stick before injection in children. Aim: The present study aimed to determine the effectiveness of a novel herbal anesthetic gel used as a topical anesthetic before an inferior alveolar nerve block. SettingsandDesign: This was a bilateral split-mouth, single blind, crossoverin vivo study. Methods: Atotal number of 30 children were selected for this study design. After the application of the topical anesthesia, a 26-gauge needle was inserted in the mucobuccal fold and local anesthetic solution was deposited. Assessment of pain perception was done before the procedure and at the time of needle penetration using hemodynamic parameters such as blood pressure and heart rate. The objective and subjective pain assessment was recoded through sound eye motor scale and Faces Pain Scale-Revised (FPS-R). StatisticalAnalysis: As the data followed a normal distribution, parametric tests were used to analyze these data. The independent sample t-test and paired sample t-test were used to check the mean differences. Results: The data showed no statistically significant differences in the objective and subjective pain assessment values of the novel herbal anesthetic gel compared to the 2% lignocaine gel. However, the intragroup comparisons of the before and during treatment results showed statistically significant results (P < 0.05). Conclusion: The novel herbal anesthetic gel was effective and safe in reducing the pain from needle insertion. Thus, setting up scientific evidence for the therapeutic usage of herbal products can, therefore, assist to develop a more efficient and alternative topical anesthetic.
Keywords: 2% lignocaine gel, , faces pain scale-revised scale, sound eye motor scale, , topical anesthetic gel
|How to cite this article:|
Mohite VA, Baliga S, Thosar N, Rathi N, Khobragade P, Srivastava R. Comparative evaluation of a novel herbal anesthetic gel and 2% lignocaine gel as an intraoral topical anesthetic agent in children: Bilateral split-mouth, single-blind, crossover in vivo study. J Indian Soc Pedod Prev Dent 2020;38:177-83
|How to cite this URL:|
Mohite VA, Baliga S, Thosar N, Rathi N, Khobragade P, Srivastava R. Comparative evaluation of a novel herbal anesthetic gel and 2% lignocaine gel as an intraoral topical anesthetic agent in children: Bilateral split-mouth, single-blind, crossover in vivo study. J Indian Soc Pedod Prev Dent [serial online] 2020 [cited 2021 May 18];38:177-83. Available from: https://www.jisppd.com/text.asp?2020/38/2/177/288221
| Introduction|| |
In the field of pediatric dentistry, the fear of a child before any dental procedure whether invasive or noninvasive is most commonly encountered. Dental fear in children has multifaceted origin; however, such fears can be managed during dental treatment if they are well intercepted and understood by the pediatric dentist. The most highly prevalent fear in pediatric patients is of intraoral injections and more precisely, fear of the pain due to needle prick, before any nerve block or infiltration. Local anesthetics are frequently used for pain management and to decrease the discomfort during any dental procedures in children.
However, the irony of this scenario is that local anesthetics, which are the most efficient drugs for pain management, are themselves associated with pain. Topical anesthetics play an intrinsic part to reduce pricking pain sensation due to needle sticks before any injection. Thus, it has always proven to be a significant requirement for many dental procedures, especially in children. An immense amount of research has been conducted on multiple topical anesthetics with relative and conflicting outcomes. Depending on the invasiveness and type of the dental treatment, it is imperative to be well acquainted with the type, frequency, and volume of topical anesthesia to be administered to accomplish maximum effectiveness, without any risk of toxicity. Although it is rare for infants and children to have local anesthetic toxicity, they may show greater risk compared to adults due to a slow rate of metabolism and elimination.
With the changing trends, there always arises a scope for an alternate medicine. According to the World Health Organization, 80% of the people in developing countries most solely rely on herbal ayurvedic medicines for primary health-care services. Plenty of herbal products are being researched extensively for various therapeutic uses, local anesthetic effect being one of them. In Ayurveda, Spilanthes calva, Spilanthes oleraceae, many Anacyclus species such as Anacylus pyrethrum, Anacyclus Clavatus, and Anacyclus valentinus have been previously used as topical and local anesthetic agents. However, the evidence-based research of herbal medicine for the local anesthetic effect is minuscule. The aim of this study was therefore to investigate the efficacy and compare the topical anesthetic effects of a herbal gel and 2% lignocaine gel in reducing pain from needle sticks.
| Methods|| |
The study design was approved by the Institutional Ethical Committee of Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha (Ref. No. DMIMS (DU)/IEC/2017-18/6745). The nMaster software (version 2.0, Christian Medical College, Vellore, India) was used to calculate the sample size. The effect size was calculated using the standard deviation and mean from the previously conducted research, error probability was 5, power (alpha error probability) was 80, and allocation ratio N2/N1 was 1. The total sample size (N) obtained was 60, with 30 in each group.
A total of 30 children were selected from the Outpatient Department of Pediatric and Preventive Dentistry at Sharad Pawar Dental College and Hospital, Wardha. The study design for this research was based on the bilateral split-mouth, single-blind, crossover study. Children aged 8–14 years requiring mandibular bilateral local anesthesia as nerve blocks were included in the study. Children with any with acute infections or systemic diseases, mentally retarded children, and patients under sedative drugs were excluded from the study. Written informed consent was acquired from the parents of all the subjects. The topical anesthetics were randomly assigned a letter: Agent X-Herbal anesthetic gel and Agent Y-2% lignocaine gel (LOX 2% JELLY].
The herbal anesthetic gel was prepared from the roots of Anacyclus pyrethrum DC and fresh flower buds of Spilanthes acmella MURR. These plants were pulverized into small parts using sieve number 10 and prepared into fine powder. The preparation of gel was done using extract of these powdered plants by continuous warm percolation using the Soxhlet apparatus. 100 gm of coarse powder (50 g of flower buds of S. acmella and 50 g of the roots of A. pyrethrum) was soaked overnight in a sufficient amount of solvent in a container using water: ethanol (99.9% absolute ethanol) in a ratio of 1:1. The gel was then prepared by mixing it with carbopol 934 in a ratio of 3:2.
Topical anesthetic X was applied on one side of the arch for the patients in Group A and anesthetic Y for patients in Group B. In the next appointment, the topical anesthetics were crossed across the two groups. The area of application was the mucobuccal fold in ramus of the mandible (anterior border). Before the application of the selected anesthetic, blood pressure (BP) cuff was attached to the left arm of the child, and BP as well as heart rate was recorded using an automatic BP and heart rate monitor (Niscomed Medical Devices, PW-215). These hemodynamic parameters for each child were recorded before the procedure and at the time of needle penetration.
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 26-gauge sterile needle was inserted until it came in contact with the bone, and then, the local anesthetic solution was deposited. During the needle penetration, BP and heart rate readings were recorded. Two trained observers recorded the sound eye motor (SEM) scale from a distance of 1.5 m from the dental operatory. The SEM scale is based on observations of the level of pain indications from comfort to pain level ranging from 1 to 4. After the procedure was over, the children were presented and described the Faces Pain Scale-Revised (FPS-R) for subjective pain assessment. From left to right, the faces ranging from 0, 2, 4, 6, 8, or 10 on the scale showed no pain and as the expression moved a score of 1 toward the right, the facial expression showed an increase in the pain. The child was asked to point out the appropriate facial expression and the score was recorded by the observer.
The statistical analysis for the comparative evaluation of the pain perception before the application of topical anesthetics and at the time of needle penetration was carried out to find the significant differences between these two topical anesthetics and their ability to reduce the pricking pain sensation due to needle stick. The software used for the analysis was Statistical Package for the Social Sciences Version 24.0 (IBM Corporation, Chicago, USA), and P < 0.05 was considered as the level of significance.
| Results|| |
On intragroup comparison of the mean systolic, diastolic BP, and heart rate of 2% Lignocaine gel group, the systolic BP shows statistically significant reduction (P = 0.036) from 108.66 ± 10.12 before application to 106.63 ± 9.86 during the needle penetration. The diastolic BP showed statistically no significant difference with P = 0.776 before and during treatment. However, the mean heart rate values in this group showed statistically significantly reduction (P = 0.001) from 91.66 ± 10.71 before application to 87.53 ± 12.55 during needle penetration [Table 1].
|Table 1: Intra-group comparison of the mean systolic, diastolic blood pressure and heart rate of 2% Lignocaine group before application and during needle penetration using paired sample t-Test.|
Click here to view
Similarly, on intragroup comparison of the mean systolic, diastolic BP, and heart rate of the herbal gel group. The systolic BP showed statistically significant reduction (P = 0.026) from 113.33 ± 9.05 before application to 111.26 ± 8.76 during the needle penetration. The diastolic BP showed no statistically significant difference with P = 0.001, and the mean heart rate values in this group showed a statistically significant reduction (P = 0.006) from 93.06 ± 11.69 before application to 88.93 ± 11.13 during needle penetration [Table 2]. However, on comparison of the mean heart rate before application and during needle penetration between the two groups, it was found that there was no statistically significant difference in mean heart rate before (P = 0.631) and during (P = 0.476) between the lignocaine and herbal gel groups [Table 3].
|Table 2: Intra-group comparison of the mean systolic, diastolic blood pressure and heart rate of Herbal gel group before application and during needle penetration using paired sample t-Test.|
Click here to view
|Table 3: Comparison of mean heart rate before and during the needle between 2% Lignocaine gel and herbal anaesthetic gel groups using independent sample t-Test.|
Click here to view
[Graph 1] and [Graph 2] show the comparison between the mean S, E, and M (Sound Eye Motor) values between 2% lignocaine gel and herbal gel. The mean S, E, and M values between the two groups and the mean FPS values indicate nonsignificant difference in mean S (P = 1.000), E (P = 0.685), and M (P = 0.675) values and the mean FPS-R values (P = 0.427) between the lignocaine and herbal gel groups [Table 4]. On the comparison of the mean systolic and diastolic BP between the 2% Lignocaine gel and herbal gel before the application, these values indicate that there is no statistically significant difference in mean systolic (P = 0.065) and diastolic (P = 0.391) BP before application between the two groups. The mean systolic and diastolic BP during the needle penetration between the two groups also shows no statistically significant difference in the mean systolic (P = 0.059) and diastolic (P = 0.805) BP.
|Table 4: Inter-group comparison of the mean systolic, diastolic blood pressure and heart rate of 2% lignocaine and herbal gel group before the application and during needle penetration using independent sample t-Test.|
Click here to view
| Discussion|| |
Local anesthesia injection is the most critical factor linked to the withdrawal of dental treatment. The fear and anxiety induced by dental injections is known as “needle phobia,” which is among the most harrowing components of dentistry for a patient. This needle phobia is associated with anxiety which can culminate in syncope as well. Reducing this fear in children can help ensure overall comfort and well-being throughout the dental treatment. Topical anesthetics induce a temporary loss of sensation on the applied surface up to a depth of 2–3 mm by hindering the passage of signals from the terminal fibers of the sensory nerves.
Various adverse effects such as overdosage, allergic reactions, ulcerations, idiopathic swelling of soft tissues,, anaphylaxis, and toxic reactions to the topically applied local anesthetics are expected to occur. The increase in the dosage could lead to high plasma concentration levels and eventually cause serious adverse effects. Thus, topical anesthetics should be used at appropriate concentration and dosage, as they might cause side effects.
Various medical literature supports the clinical efficacy of herbal plants in pharmaceutical medicinal researches.A. pyrethrum is a plant that belongs to Asteraceae family commonly known as Akarkara, in the Indian ayurvedic medicine. Several experimental studies have been done on A. pyrethrum and it has been used for its multiple biological actions such as antibacterial, anti-arthritic, antiviral, antibiotic, immunostimulatory, emmenagogue, sialagogue, local anesthetic, and antioxidant.
The cortical portion of the root contains about 5% of the acrid compound called pyrethrin (pellitorine), which is responsible for the various medicinal values of this plant, especially its local anesthetic activity. Sujith et al. demonstrated the local anesthetic effect of 2% aqueous and alcoholic extract of A. pyrethrum greater than lignocaine (0.2%). They confirmed that the local anesthetic activity from the root extract of this plant was mainly due the active constituent in this plant, an alkaloid, pyrethrin, which yields pyrethric acid. Venkatakrishna-Bhatt et al. conducted a toxicity analysis with aqueous extract of A. pyrethrum in mice and they concluded that a maximum dose of 750 mg/kg is safe to be used local anesthesia. Patel et al. also observed that the 2% concentration of the ethanolic extract of A. pyrethrum roots promoted anesthesia and produced a pterygomandibular block when compared with xylocaine and it was found to be safe toxicologically without any side effects.
S. acmella (Compositae or Asteraceae) is a genus comprising more than 60 species which are widely distributed in the subtropical and tropical regions of the world, such as Africa, Sri Lanka, Borneo, America, and India. Another variant of this plant is also known as Jambu or watercress (Acmella oleracea) with anesthetic and analgesic properties which have been proven to be helpful to treat many oral lesions. On chewing the leaves and flowers of this plant, a tingling sensation is experienced followed by numbness of the lips and tongue. Major isolates of S. acmella are lipophilic alkylamides or alkamides bearing different number of unsaturated hydrocarbons such as spilanthol or affinin (2E,6Z,8E)-N-isobutyl-2, 6, 8-decatrienamide and amide derivatives.
Spilanthol, an isobutylamide compound, is the major constituent that has the action of local anesthesia. Santana de Freitas-Blanco et al. conducted anin vivo trial to test for a novel mucoadhesive film containing A. oleracea extract for its efficacy as topical anesthetic. Chakraborty et al. studied the local anesthetic activity of aqueous extract S. acmella in animal models through intracutaneous wheal in guinea pigs and plexus anesthesia in frogs. Both these studies found that the significant activity of the S. acmella was due to the production of alkylamides. The well-known local anesthetics consist mainly of amide agents, for instance, xylocaine with mechanism of action involving the blockage of Na + channels. The alkylamides found in S. acmella also produced local anesthetic action by blocking the Na + channels.
The use of topical anesthetics in younger children has a possibility of increased risk of toxicity as compared to adults, as the metabolism and elimination of the agent can be delayed in young children, owning to less weight and different pharmacokinetic characteristics. Pain perceptions vary greatly based on the onset, intensity, and degree of tolerance of the child. Thus, it can become very difficult to measure the perception of pain in children. Hence, a controlled in-use-data would be largely beneficial in children.
Topical anesthesia is effective when applied on the site for an adequate duration of time and a lower duration of application might not produce the desired clinical effect. Different investigations have used 30 s to 20 min time of application. However, no relationship was found where the duration of application of topical anesthesia and increased clinical effectiveness were directly proportional. Anxiety is a special variety of fear and that is experienced in anticipation of threatening stimuli, which is associated and directly reflected through changes in the BP and heart rate. The fear of needles and syringes in children has been one of the major causes of anxiety which eventually results in psychological stress and negative consequences.
The cardiovascular system is affected by the autonomic nervous system (ANS) as well as endocrinological factors. In the present study, BP and heart rate were measured before the application of the topical anesthetics and during the needle penetration to evaluate the changes in the hemodynamic. The reduced levels of the systolic BP were under the physiologic limits and in accordance to the study conducted by Joshi et al. who reported a significant decrease in the relationship between systolic and diastolic BP after the application of prilido 5% cream and lignocaine 2% gel to reduce the pricking pain response.
The change in the heart rate of the children indicated that there was a reduction in the mean heart rate before the application of the gel and during the needle penetration within each group, but on comparison of both the groups with each other, the difference was found to be nonsignificant. These results were in accordance with the study conducted by Lucas Cerutti de Andrade et al. who aimed at determining the effectiveness of the ointment with A. oleracea and 20% benzocaine as topical anesthetic for the buccal mucosa. They reported that no statistically significant difference was found when comparing the alteration of heart rate after application in both the groups. Joshi et al. also concluded that no statistically significant difference in the mean heart rate was found between the two groups.
During stressful occurrences, the ANS responds with an adrenergic discharge, which is originated by the sympathetic activation and adrenal hormone release. BP and heart rate are physiologic parameters which are directly altered by the adrenalin discharge. The heart rate and the BP were thus registered priorly and monitored during the needle penetration. Pain is a complex and not entirely understood behavioral phenomenon. Behavioral pain response scores by direct observation, reports from the child, and physiological measurements are three main methods of determining dental anxiety and behavioral issues during regional anesthesia administration.
The mean SEM values and FPS-R on comparison between the two groups indicated that both the groups equally reduced pain as their values were similar. These results were in accordance to the study conducted by Lucas Cerutti de Andrade et al., as they also found no statistically significant difference in the pain rating using SEM scale. Joshi et al. compared the SEM scale after treatment with 5% prilido cream and 2% lignocad gel and found statistically significant association (0.000) with P < 0.05 between the two groups. The FPS-R scale includes quantitative scores to reflect the suffering of a child so that the statistical measurements could indicate the child's level of pain. Gill and Orr showed non-significant difference between applications of topical anesthetic and placebo. Since they used a 5-point descriptive scale for pain assessment, they may not have noted the difference between topical anesthetics and placebo.
The main interests of this study rest on both the methodology, which was a bilateral split-mouth, single-blind, crossover study. This study design minimized the risk of bias in the study population, which was composed of children. The self-report of a child for pain assessment is generally considered a “gold standard” for pain evaluation. The 6–8 year old children reported by Bieri et al. had understood the term pain and its different pain levels clearly. Several factors affecting the perception of pain are difficult to measure and assess, including developmental factors and prior pain experience. However, this study included both physiological parameters such as BP and heart rate and descriptive and observational scales such as FPS-R and SEM. Thus, testing the results through these parameters made this study more accurate and precise in terms of results and observations.
| Conclusion|| |
The following conclusions were inferred from the present study:
- 2% lignocaine gel proved to effective in reducing pain due to needle stick
- Herbal anesthetic gel proved to be effective in reducing pain due to needle stick
- 2% lignocaine gel and herbal anesthetic gel were equally effective in reducing pain due to needle stick prior to administration of inferior alveolar nerve block.
Financial support and sponsorship
This study was financially supported by ntramural grant program of Datta Meghe Institute of Medical Sciences.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Gao X, Hamzah SH, Yiu CK, McGrath C, King NM. Dental fear and anxiety in children and adolescents: Qualitative study using YouTube. J Med Internet Res 2013;15:e29.
Al-Omari WM, Al-Omiri MK. Dental anxiety among university students and its correlation with their field of study. J Appl Oral Sci 2009;17:199-203.
Priyatham S, Nuvvula S. Intraoral topical anaesthesia in pediatric dentistry: Review. Int J Pharma Bio Sci 2016;7:346-53.
Muralikrishnan K, Asokan S, Geetha Priya PR, Zameer Ahmed KS, Ayyappadasan G. Comparative evaluation of the local anesthetic activity of root extract of Anacyclus pyrethrum and its interaction at the site of injection in guinea pigs. Anesth Essays Res 2017;11:444-8.
] [Full text]
Kumar VK, Lalitha KG. Pharmacognostical studies on the root of Anacyclus pyrethrum DC. Indian J Nat Prod Resour 2012;3:518-26.
Prachayasittikul V, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. High therapeutic potential of Spilanthes acmella: A review. EXCLI J 2013;12:291-312.
Usmani A, Khushtar M, Arif M, Mohd S, Sing S, Mujahid M. Pharmacognostic and phytopharmacology study of Anacyclus pyrethrum: An insight. J Appl Pharm Sci 2016;6:144-50.
Kosaraju A, Vandewalle KS. A comparison of a refrigerant and a topical anesthetic gel as preinjection anesthetics: A clinical evaluation. J Am Dent Assoc 2009;140:68-72.
Lodaya R, Bhat C, Gugwad SC, Shah P, Shirol D. Clinical evaluation of transcutaneous electrical nerve stimulation [TENS] for various treatment procedures in pediatric dentistry. Int J Clin Dent Sci 2010;1:20-5.
Graham DT. Prediction of fainting in blood donors. Circulation 1961;23:901-6.
Kreider KA, Stratmann RG, Milano M, Agostini FG, Munsell M. Reducing children's injection pain: Lidocaine patches versus topical benzocaine gel. Pediatr Dent 2001;23:19-23.
Yaman Z, Kişnişci RS. Idiopathic swelling of the lower lip associated with topical anaesthesia. Report of three cases. Aust Dent J 1998;43:324-7.
Kumar DM. Management of anaphylaxis in dental office-an update. Int J Pharm Bio Sci 2015;6:401-7.
Mohite V, Baliga S, Thosar N, Rathi N. Role of dexmedetomidine in pediatric dental sedation. J Dent Anesth Pain Med 2019;19:83-90.
World Health Organization. General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine, HO/EDM/TRM/2000. I, Geneva: World Health Organization; 2000. p. 74.
Canlı K, Yetgin A, Akata A, Altuner EM. Antimicrobial activity and chemical composition screening of anacyclus pyrethrum root. Indian J Pharm Educ 2017;51:244-8.
Sujith K, Darwin R, Suba V. Toxicological evaluation of ethanolic extract of Anacyclus pyrethrum in albino wistar rats. Asian Pac J Trop Dis 2012;2:437-41.
Kameshwaran M, Ayyappadasan G. Anesthetic, antioxidant and antibacterial activities of anacyclus pyrethrum root extract – AnIn vitro
animal study. Int J Ayu Pharm Chem 2017;7:127-37.
Venkatakrishna-Bhatt H, Panchal GM, Patel VK. Toxicity of A. Pyrethrum in mice. Curr Sci 1988;57:912-23.
Patel VK, Patel RV, Venkatakrishna-Bhatt H, Gopalakrishna G, Devasankariah G. A clinical appraisal of Anacyclus pyrethrum root extract in dental patients. Phytother Res 1992;6:158-9.
Prachayasittikul S, Suphapong S, Worachartcheewan A, Lawung R, Ruchirawat S, Prachayasittikul V. Bioactive metabolites from Spilanthes acmella Murr. Molecules 2009;14:850-67.
Dubey S, Maity S, Singh M, Saraf SA, Saha S. Phytochemistry, pharmacology and toxicology of spilanthes acmella: A review. Adv Pharmacol Sci 2013;2013:423750.
Santana de Freitas-Blanco V, Franz-Montan M, Groppo FC, de Carvalho JE, Figueira GM, Serpe L, et al
. Development and evaluation of a novel mucoadhesive film containing acmella oleracea extract for oral mucosa topical anesthesia. PLoS One 2016;11:e0162850.
Chakraborty A, Devi BR, Sanjebam R, Khumbong S, Thokchom IS. Preliminary studies on local anesthetic and antipyretic activities of Spilanthes acmella Murr. in experimental animal models. Indian J Pharmacol 2010;42:277-9.
] [Full text]
Yokoi T. Essentials for starting a pediatric clinical study (1): Pharmacokinetics in children. J Toxicol Sci 2009;34 Suppl 2:SP307-12.
Malamed SF. Handbook of Local Anaesthesia. 6th
ed. Mosby, St. Louis: Elsevier Health Sciences; 2014. p. 33-43.
Carr MP, Horton JE. Clinical evaluation and comparison of 2 topical anesthetics for pain caused by needle sticks and scaling and root planing. J Periodontol 2001;72:479-84.
Rathi NV, Khatri AA, Agrawal AG, M SB, Thosar NR, Deolia SG. Anesthetic Efficacy of Buccal Infiltration Articaine versus Lidocaine for Extraction of Primary Molar Teeth. Anesth Prog 2019;66:3-7.
Kaufman E, Epstein JB, Naveh E, Gorsky M, Gross A, Cohen G. A survey of pain, pressure, and discomfort induced by commonly used oral local anesthesia injections. Anesth Prog 2005;52:122-7.
Brand HS, Abraham-Inpijn L. Cardiovascular responses induced by dental treatment. Eur J Oral Sci 1996;104:245-52.
Joshi P, Baliga S, Rathi N, Thosar N. Comparative evaluation of pricking pain response, behavioural response, heart rate and blood pressure response to prilido cream and lignocad gel prior to local anesthesia administration in children. IOSR J Pharm Biol Sci 2015;10:37-41.
de Andrade LC, Rotta IW, Chaves SR, Uchida DT, Gazim ZC, Ferreira FB, et al
. Effectiveness of Acmella oleracea for topical anesthesia on buccal mucosa. Rev Odonto Cienc 2013;28:61-5.
Gill CJ, Orr DL 2nd
. A double-blind crossover comparison of topical anesthetics. J Am Dent Assoc 1979;98:213-4.
Bieri D, Reeve RA, Champion GD, Addicoat L, Ziegler JB. The faces pain scale for the self-assessment of the severity of pain experience by children: Development, initial validation, and preliminary investigation for ratio scale properties. Pain 1990;41:139-50.
[Table 1], [Table 2], [Table 3], [Table 4]