|Year : 2015 | Volume
| Issue : 2 | Page : 125-128
Achieving pulpal anesthesia with a topical anesthetic paste
Bradley Carn, Cyril Pandarakalam, Dana Jackson, Christa Hopp, Kevin Rowland
Applied Dental Medicine, Southern Illinois University, School of Dental Medicine, 2800 College Avenue, Alton, IL 62002, USA
|Date of Web Publication||17-Nov-2015|
Dr. Kevin Rowland
Southern Illinois University, School of Dental Medicine, 2800 College Avenue, Alton, IL 62002
Source of Support: None, Conflict of Interest: None
Aim: The efficacy of a topically applied formulation of tetracaine base (6%) was investigated against benzocaine in achieving pulpal anesthesia in a randomized, placebo-controlled, double-blind study. Materials and Methods: Subjects' baseline pulpal responses to an electric pulp tester were measured, followed by a 10 min application of either tetracaine anesthetic paste (TAP), benzocaine (20%), or placebo. Treatments were removed and pulp testing was performed at 10 min, 15 min, and 20 min postapplication. Results: TAP produced significant pulpal anesthesia at 184% ± 7.2% above baseline versus 14% ± 1.7% above baseline for benzocaine at 15 min (P < 0.03). Differences between treatments were tested with the Wilcoxon test and the Steel-Dwass test, which is the nonparametric version of the all-pairs Tukey's honestly significant difference test. Conclusion: Achieving profound anesthesia with a topical anesthetic paste could lead to injection less procedure, improved postsurgical incisional pain management, and ameliorate pain associated with a variety of lesions.
Keywords: Anesthetic, orofacial pain, pulp, topical
|How to cite this article:|
Carn B, Pandarakalam C, Jackson D, Hopp C, Rowland K. Achieving pulpal anesthesia with a topical anesthetic paste. J Orofac Sci 2015;7:125-8
|How to cite this URL:|
Carn B, Pandarakalam C, Jackson D, Hopp C, Rowland K. Achieving pulpal anesthesia with a topical anesthetic paste. J Orofac Sci [serial online] 2015 [cited 2021 Oct 26];7:125-8. Available from: https://www.jofs.in/text.asp?2015/7/2/125/169775
| Introduction|| |
Injections are often preceded by application of topical anesthetic agents to reduce the pain associated with the injections. Topical anesthetics are often ineffective in providing even soft tissue anesthesia  and have a short duration of action. ,, While some procedures can be accomplished via topical anesthetics alone such as scaling and root planning and palliative treatment of superficial mucosal lesions, more invasive procedures require infiltration or nerve block to obtain anesthesia. Benzocaine is the most commonly used topical anesthetic in dentistry, but, recently has come under considerable scrutiny by the Food and Drug Administration (FDA) due to the potential of inducing serious methemoglobinemia, especially in young patients.  Methemoglobinemia results in a leftward shift of the oxyhemoglobin curve due to an increased binding affinity of hemoglobin for oxygen which makes unloading of oxygen to tissues more difficult. , Additionally, topical anesthetic formulations which contain multiple active agents can have serious adverse effects, a critical problem which has received attention from the FDA. 
Tetracaine, an ester anesthetic, is widely used in medicine, especially in the fields of dermatology, otolaryngology, and ophthalmology. Topical tetracaine is generally considered as safe and effective, , but is typically used in combination with other active agents. Tetracaine with adrenaline and cocaine and lidocaine/prilocaine/tetracaine (profound) are two oral tetracaine-containing anesthetic formulations available through compounding pharmacies, which are not regulated or quality assessed.
The current study is designed to test the anesthetic efficacy of a unique formulation of an anesthetic paste in a randomized, double-blind, placebo-controlled trial. Tetracaine anesthetic paste (TAP) is formulated as a topical, intraoral anesthetic containing 6% tetracaine as the sole, active ingredient. TAP contains propylene glycol as a putative penetration enhancer, , carrier vehicles, and a mucoadhesive. In a previous study, the effectiveness of TAP in reducing pain associated with palatal injections was compared to topical benzocaine through subjective interpretation on a pain scale of 0-9, where TAP performed at least as well as benzocaine.  Although TAP has been shown to anesthetize the relatively thin palatal mucosa, we sought to investigate the efficacy of TAP to achieve anesthesia of deeper tissues such as the dental pulp. In the current study, we postulated that TAP would outperform benzocaine in an objective measure of pulpal pain.
| Materials and Methods|| |
The study was conducted at the University's Oral Medicine's Oral Diagnosis Clinic and approved by the Institutional Review Board. Dental students were recruited as participants for the study and informed consent was obtained from each participant. Exclusion criteria included presence of obvious carious lesions or restorations, allergies to anesthetics, individuals with systemic diseases (hypertension, diabetes, autoimmune disorders, etc.,), pregnancy, or breastfeeding. A total of 47 subjects were randomized by computer software into the following groups: TAP (n = 21), benzocaine (n = 19), and placebo (n = 7). The placebo test material was a formulation consisting of all materials found in TAP except the active ingredient, 6% tetracaine. The number of participants in each group was selected based upon our estimations of sample size to reach a 95% confidence interval. Preliminary participant evaluation included a focused medical history and physical examination, including blood pressure and pulse measurements. Baseline pain threshold levels of participants were recorded by evaluating the responses to an electric pulp tester (Parkell Digitest). The electrical pulp tester was calibrated by the manufacturer and was confirmed by the investigators by recording the time, voltage output, and display parameters at the end of the experiment. Electrical stimuli were applied by lightly touching the stimulus probe to the facial surface of tooth #6 or, in one instance, tooth #11, in the middle third of the clinical crown in both the apicocoronal and mesiodistal dimensions. After acquiring baseline pulpal responses, randomly assigned, predetermined test materials (15 mg) were applied to the mucosa over the canine eminence of tooth #6, which most closely approximated the apex of the tooth by using sterile cotton-tipped applicators. Ten minutes postapplication, test materials were wiped off with sterile gauze, rinsed with water, and the area was dried with sterile gauze. Immediately, following the removal of the anesthetic, the tooth was dried and tested with the electric pulp tester, using toothpaste as a conduction medium, at 5 min intervals for a total of 20 min.
Pulpal responses at 10, 15, and 20 min postapplication were divided by each participant's recorded baseline pulpal response and the averages of all participants' pulpal responses at each time point were calculated. Data distributions were tested for normality with the Shapiro-Wilk W-Test. Multivariate repeated measures analysis of variance was used to test for differences between the treatments through time. Three time points were used as within-subject (repeated measures) factors and treatment was the between-group factor. The homogeneity of variances assumption was tested with the Cochran C, Hartley, Bartlett, and Box M-tests. Differences between treatments were also tested with the Wilcoxon test and the Steel-Dwass test, which is the nonparametric version of the all-pairs Tukey's honestly significant difference test.
| Results|| |
Tetracaine anesthetic paste significantly increased pain thresholds
TAP-treated subjects reached the maximum current output of the electric pulp testing (EPT) in 4 out of 21 patients (19.0%) at the 15 min time interval. In contrast, no subject reached the maximum current output of the EPT in either the benzocaine or placebo group.
Average percentage above baseline responses in the TAP group were 31% ± 1.2%, 184% ± 7.2%, and 51% ± 1.8% higher than baseline at 10, 15, and 20 min, respectively [Figure 1]. Average percentage above baseline responses in the benzocaine group were 4% ± 0.7%, 14% ± 1.7%, and 2.0% ± 0.8% higher than baseline at 10, 15, and 20 min, respectively. Average percentage above baseline responses in the placebo group were 47% ± 5.4%, 35% ± 2.8%, and 58% ± 3.0% higher than baseline at 10, 15, and 20 min, respectively.
|Figure 1: Average percentage above baseline electric pulp test responses for subjects administered tetracaine anesthetic paste, benzocaine, and placebo for 10 min above the canine eminence of tooth #6. Data are expressed as means ± standard error. (*tetracaine anesthetic paste vs. benzocaine at 15 min; P > 0.035; Wilcoxon test)|
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Maximum anesthetic efficacy was achieved after 15 min
At the 15 min time point, average percentage above baseline responses in the TAP group were significantly higher than the responses in the benzocaine group (184% ± 7.2% vs. 14.0% ± 1.7%; P = 0.0351). No statistically significant differences were demonstrated between the TAP and the placebo group (P = 0.47) or between benzocaine and the placebo groups (P = 0.68). Based upon our calculations, a sample size of 53 in each group would be needed to demonstrate the differences between all the three groups.
| Discussion|| |
Our results indicate that TAP is effective in producing pulpal anesthesia likely due to tetracaine's potent anesthetic potential, coupled with the penetrating and mucoadhesive properties of the paste. In a previous study, the effectiveness of TAP in reducing pain on palatal injections was compared to benzocaine through the subjective interpretation of the patient using a pain scale of 0-9, where TAP performed as well as benzocaine.  In the current study, TAP application for 10 min was effective in producing significant pulpal anesthesia and significantly outperformed benzocaine. The investigators noted that the mucoadhesive nature restricted TAP to the application site significantly better than benzocaine. The authors theorize that this may have contributed to the improved efficacy in the TAP-treated group due to increased contact time and subsequent increased diffusion of the anesthetic across the mucosa.
Evaluation of pain to maxillary labial vestibular infiltration after application of TAP measured by visual analog scale (VAS) was considered as an experimental design. However, due to the psychology of repeat needle injections, variability of needle placement, speed and depth of penetration, and variability of angulations, this was thought to be a substandard approach to obtain repeatable and quantifiable levels of pain induction. Additionally, the VAS is a subject to unquantifiable interpretation of pain that EPT is not as VAS that requires the additional cognitive step of interpreting quantity of pain and placing it on the scale. It is for the aforementioned reasons that EPT was the chosen modality for pain induction. While research exists indicating that EPT is an inherently poor predictor of pulpal integrity or health, EPT is adequate to establish a quantitative baseline for induction of pain.
Tetracaine is one of the most commonly used topical anesthetics for extraoral use. Heat-assisted delivery of 4% tetracaine (Ametop) alone and a mixture of 7% tetracaine/7% lidocaine are equally effective for intravenous cannulation.  A similar delivery of 1:1 mixture of lidocaine and tetracaine for local anesthesia for minor dermatological procedures in elderly patients was found to be safe and effective.  The use of 8% tetracaine topically in providing tympanic membrane anesthesia for myringotomy procedure has also been found to be highly efficacious and safe. 
Despite strong evidence for tetracaine's safety and efficacy, tetracaine is rarely used intraorally. When studied intraorally, a compound mixture of 4% tetracaine, 20% lidocaine, and 2% phenylephrine was found to be more effective than Oraqix and 20% benzocaine for placement of temporary anchorage devices for orthodontic purposes , and liposome encapsulated tetracaine, was more effective than eutectic mixture of local anesthetic (EMLA).  Our results are comparable to experiments that achieved pulpal anesthesia (tooth #6) by continuous EMLA (lignocaine 2.5% and prilocaine 2.5%) application throughout the testing period.  Responses in that study were not evaluated for statistical significance. Pulpal anesthesia in the present study was transient and short-lived. The transient nature is owed to the removal of the anesthetic before testing. The fact that tetracaine has strong vasodilatory actions  and likely increased hematogenous pseudocholinesterase metabolism which limited anesthetic duration. We postulate that an extended application period and addition of a vasoconstrictor such as epinephrine may significantly extend the period of pulpal anesthesia.
Placebo responses were highly variable in the present study, and, on average, produced some degree of anesthesia similar to placebo responses in a prior study using an electric pulp tester.  Use of electrical stimulation to increase tooth pain thresholds have been observed. , Anesthesia following electrical stimulation of the teeth has been explained by activation of β fibers inhibiting the conduction of painful signals to higher centers through a centralized gating mechanism. Additionally, release of endorphins through endogenous stress responses  may participate in the phenomenon. For placebo testing, the individuals' expectations of the outcome contribute to the response and are known as "response expectancy." ,, For example, in a study of sham electroacupuncture to relieve arthritic pain, a positive expectation prior to the start of testing was significantly correlated to a benefit in the reduction of pain, but clinically relevant pain reduction was only experienced in the "true" electroacupuncture group.  We argue that a positive response expectation existed in the placebo group, as part of the informed consent process, and contributed to an increase in pain thresholds. Also, test subjects were dental students who were aware of TAP and its purported efficacy which may have elevated response expectations. In the benzocaine group, however, the expectation of pain may be higher during the testing phase because of the rapid resolution of anesthesia in the soft tissue.
Overall, the ability of a topically applied anesthetic in producing pulpal anesthesia is significant and may eventually lead to intraoral procedures being performed without the use of injectable anesthetics. Further investigation of TAP in the palliative treatment of aphthous ulcers, herpetic stomatitis, traumatic ulcers, erosive lichen planus, and oral mucositis is warranted. Investigation into the procedural suitability for biopsy, nasopharyngoscopy, gingivectomy, operculectomy as well as dermatologic applications, especially for pediatric trauma, is also indicated.
Financial support and sponsorship
Southern Illinois University. The anesthetic discussed in the manuscript was kindly provided by Pharmadent. We would like to thank Dr. Charles Hildebolt for providing expert technical assistance. We would also like to thank Dr. Anita Joy for reading an earlier version of the manuscript.
Conflicts of interest
There are no conflicts of interest. Dr. Rowland is a consultant for Pharmadent.
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