1. Introduction
Articaine has demonstrated significantly higher success rates (40–88%) compared to lidocaine (10–71%) in both healthy teeth and cases of irreversible pulpitis [
1,
2,
3,
4]. Despite these clinical observations, the precise mechanism underlying articaine’s enhanced efficacy in mandibular infiltrations remains poorly understood.
Several hypotheses have been proposed to explain articaine’s superior anesthetic activity. The unique chemical structure of articaine, specifically the presence of a thiophene ring and an intra-molecular hydrogen bond, along with its high concentration (4%), are thought to enhance its ability to penetrate the dense mandibular cortical bone. Additionally, articaine’s increased lipophilicity improves its tissue penetration, which is particularly advantageous in terms of achieving effective anesthesia in challenging cases. These combined chemical modifications contribute to articaine’s enhanced efficacy compared to other anesthetics [
5,
6,
7]. Comparative studies have evaluated the efficacy of articaine, lidocaine, and prilocaine, all at a 4% concentration, in the primary buccal infiltration of healthy mandibular molars [
1,
5,
6,
7]. These studies consistently report that articaine achieves the highest success rates.
Lidocaine and articaine are both amide-type local anesthetics commonly used in dental practice [
8]. Lidocaine, classified as an FDA Category B drug, is known for its reliable efficacy and safety profile. Articaine, an FDA Category C drug, has a unique molecular structure with a thiophene ring, enhancing its lipid solubility and potency. Articaine’s higher potency allows for better bone penetration, which is particularly advantageous in buccal infiltrations [
9]. However, articaine’s increased potency also raises concerns about its toxicity, necessitating careful consideration when choosing an anesthetic agent. These differences in potency, efficacy, and FDA classification underline the importance of our comparative study [
10].
Based on previous studies, there are conflicting findings regarding the effectiveness of lidocaine and articaine. One study showed that using 4% articaine for both the IANB (inferior alveolar nerve block) and buccal infiltration resulted in a higher success rate in terms of achieving pulpal anesthesia compared to using 2% lidocaine [
11]. However, a systematic review and meta-analysis suggested that both anesthetics provide similar outcomes when used with similar methodologies [
12]. This difference in results requires further investigation. Based on these contrasting findings, the author’s hypothesis aims to determine whether 4% articaine indeed offers better anesthetic efficacy compared to 2% lidocaine, specifically in patients with symptomatic irreversible pulpitis.
The anatomical features of the mandible, such as the mental foramen (MF) and accessory foramina, may also influence the effectiveness of buccal infiltration [
6,
13]. Articaine’s distinct chemical composition compared to other amide-type anesthetics could facilitate its diffusion through the thick cortical bone, potentially allowing it to penetrate the mental and incisive foramina more effectively [
14,
15,
16]. This anatomical facilitation might contribute to the higher success rates observed with articaine.
Additionally, the concentration of articaine alone has been reported to have no direct impact on its efficacy [
15]. Instead, the anatomical characteristics of the mandible are believed to play a critical role in the diffusion path of the articaine solution. Despite these insights, the authors have systematically measured these mandibular structures and correlated them with the anesthetic efficacy of articaine using advanced imaging techniques like cone beam computed tomography (CBCT).
This study aims (1) to compare the anesthetic efficacy of 4% articaine buccal infiltration in patients diagnosed with symptomatic irreversible pulpitis in mandibular molars and (2) to evaluate the influence of anatomical structures, such as the thickness of the buccal cortical bone and the distance to the mental foramen, on the efficacy of articaine infiltration using CBCT.
The null hypothesis (H0) states that “There is no significant difference in the anesthetic efficacy of 4% articaine buccal infiltration compared to the buccal cortical bone thickness in patients with mandibular molar irreversible pulpitis.”
2. Materials and Methods
2.1. Ethical Considerations and Participant Consent
This randomized controlled trial was approved by the Ethics Committee in Research of Piracicaba Dental School, University of Campinas (protocol 073/2009). Written informed consent was obtained from each participant. All data were handled confidentially and anonymized for analysis.
2.2. Study Design and Participants
This study evaluated the efficacy of 4% articaine buccal infiltration (n = 30) in patients with mandibular molar irreversible pulpitis; establishing a control group, the authors chose 2% lidocaine to perform the inferior alveolar nerve block (n = 20) (
ClinicalTrials.gov Identifier: NCT01912755). Fifty patients referred to the emergency center of Piracicaba Dental School were diagnosed with symptomatic irreversible pulpitis in the first or second mandibular molars. The study followed the CONSORT 2010 guidelines to ensure the robustness and transparency of the trial design and reporting (
Figure 1) [
17].
2.3. Inclusion and Exclusion Criteria
This study included patients who met specific inclusion criteria to ensure the consistency and reliability of the results. Participants were required to be 18 years of age or older. They must not have used any analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) recently, as these could alter their pain perception and interfere with the study’s outcomes. Eligible patients experienced long-lasting spontaneous pain, rated as moderate to severe, during cold testing with EndoFrost (Coltene-Roeko, Langenau, Germany). Additionally, the presence of bleeding coronal pulp upon access opening was necessary for inclusion. Radiographically, patients were required to exhibit the absence of periapical radiolucency, except for a widened periodontal ligament.
Patients were excluded from the study if they had non-endodontic diagnoses or were using medications that could interfere with the trial. Pregnancy was also a criterion for exclusion, as well as any classification other than ASA I or II, according to the American Society of Anesthesiologists (ASA) classification system. These criteria were set to maintain the integrity and focus of the study, ensuring that only appropriate candidates were evaluated to assess the efficacy of articaine in mandibular posterior infiltration.
2.4. Sample Size and Randomization
The sample size calculation indicated that 19 volunteers per group would provide the 90% power required to detect an anticipated 50% difference in success rate, with a significance level of 5%. The 50% difference was chosen based on substantial differences in success rates observed in prior studies comparing the efficacy of 4% articaine buccal infiltration to 2% lidocaine nerve block, particularly in cases of irreversible pulpitis [
4,
11]. To account for potential dropouts and ensure robustness, the authors aimed to recruit a total of 50 participants diagnosed with symptomatic irreversible pulpitis.
Patients were randomized into two groups using computer-generated random numbers in Microsoft Excel (Version 15.0). The randomization process involved generating a sequence of random numbers, which were then used to assign participants to either the articaine or lidocaine group. Allocation concealment was ensured by using opaque, sealed envelopes, which were prepared by an independent third party not involved in the study to maintain blinding. This method helped to prevent selection bias and ensure the integrity of the randomization process.
2.5. Intervention
A trained endodontist administered either (1) 1.8 mL buccal infiltration of 4% articaine with 1:100,000 epinephrine (articaine 100; DFL, Rio de Janeiro, RJ, Brazil), or (2) 1.8 mL inferior alveolar nerve block of 2% lidocaine with 1:100,000 epinephrine (alphacaine 100, DFL, Rio de Janeiro, RJ, Brazil).
2.6. Pain Assessment
2.6.1. Thermal Sensitivity Test
The thermal sensitivity test for diagnostic purposes was conducted by applying a cold spray (Endo-Frost, Wilcos, Rio de Janeiro, RJ, Brazil) to a small cotton pellet positioned on the cervical region of the tooth being examined. The stimulus was removed when the patient reported pain or showed no response. This test was also performed on a homologous vital tooth or an adjacent vital tooth if the homologous tooth was absent. Patients who presented with severe and long-duration pain were included in the study.
2.6.2. Electric Pulp Tester
To ensure the assessment of anesthesia, an electric pulp tester (Vitality Scanner 2006, SybronEndo, Orange, CA, USA) was used. After administering anesthesia, the pulp tester was used every 5 min up to a maximum of 10 min to confirm anesthesia. When there was an absence of pain perception at the maximum stimulus of the pulp tester, the tooth was considered anesthetized.
2.6.3. Visual Analog Scale (VAS)
Pain was assessed using a VAS, which, although subjective, provided a standardized method for patients to report and record their pain levels [
18,
19]. Each participant received a sheet containing four modified VASs. These scales consisted of a 144 mm line with “no pain” at the left end and “worst possible pain” at the right end. Participants recorded their pain before diagnosis (for data calibration), after the thermal pulp sensitivity test, and 5 and 10 min after the anesthetic’s application.
Pain intensities were classified by dividing the scale into four intervals: absent (no pain); mild (VAS score from 0 to 48 mm); moderate (VAS score from 48 to 96 mm); and severe (VAS score from 96 to 144 mm). Participants were asked to indicate the level of pain they experienced by marking a vertical line on the VAS. The distance between the starting point (marked as a 0) and the participant’s mark was then measured with a ruler, providing a numerical value to represent the intensity of the pain.
2.7. Success Criteria
The primary outcome was achieving pain-free treatment after buccal infiltration using articaine, defined as completing the endodontic procedure without the patient reporting any pain (VAS score = 0).
2.8. Cone Beam Computed Tomography (CBCT) Analysis
Twenty-seven patients from the articaine group underwent CBCT scans (iCat, Imaging Sciences International, Hatfield, PA, USA) for other dental procedures and were included in the present study. In the measurement of the coronal slices, CBCT scan images were used to determine the buccal cortical bone thickness and the distance between mesial/distal apices and the same buccal cortical bone (
Figure 2M1–AS). Axial slices were used to measure the distance between the injection site (1st or 2nd molar) and the mental foramen (
Figure 2AS).
2.9. Imaging and Measurement Analysis
CBCT scans were performed using the iCat Imaging Sciences International device (Hatfield, PA, USA) with the following parameters: 69 μSv effective dose, 6/17 cm field of view, 36.12 mA/s tube current, and 120 kVp. The voxel size was set to 0.25 mm for high-resolution imaging. Measurements were conducted using Xoran software (Xoran Technologies® Inc., Ann Arbor, MI, USA). The validation of measurements was ensured by performing each measurement in triplicate, with at least one month between sessions. The intraclass correlation coefficient (ICC) for measurement reproducibility was 0.9931 (p < 0.0001), indicating excellent reliability. The error margin for measurements was maintained within 0.25 mm, which is the voxel size used for imaging.
2.10. Statistical Analyses
Anesthetic efficacy was analyzed using Fisher’s exact test (BioEstat 5.0, Instituto Mamirauá, Belém, PA, Brazil, 2007; GraphPad Prism 6.0, GraphPad Software, San Diego, CA, USA). CBCT measurements (cortical bone thickness, distances between apices and cortical bone, and between molars and mental foramen) were analyzed using ANOVA one-way and Fisher’s LSD test. The VAS scores were evaluated using the Mann–Whitney test to perform comparisons between the groups at each time point (calibration, EndoFrost, 5 min, and 10 min). The same test was used to evaluate differences in cortical bone thickness and root distance to the cortical bone between successful and unsuccessful cases of articaine anesthesia. The Friedman test was applied to assess differences within the same group across different time points. Identical letters indicate no statistical difference between them. The significance level was set to 5% (α = 0.05) for all analyses.
3. Results
This study included 30 patients who received articaine and 20 patients who received lidocaine. Among the articaine group, 83.3% were female, and 16.7% were male; in the lidocaine group, 80% were female, and 20% were male. The average age of patients in the articaine group was 28 years (±13.8), while the average age in the lidocaine group was 33.5 years (±16.5).
Regarding the visual analog scale (VAS) results, five minutes after injection, patients in the articaine group reported an average VAS score of 41.8 (75.7%), compared to 26 (55.0%) in the lidocaine group. Ten minutes after injection, the average VAS score in the articaine group was 0 (57.0%), while in the lidocaine group it was 10.9 (54.5%).
There was no statistical difference between the groups that received articaine and lidocaine (Mann–Whitney test,
p > 0.05) at any of the time points when pain scores were recorded using the visual analog scale (VAS). However, when we looked at the VAS results separately, we found that the VAS scores for EndoFrost were significantly different (Friedman test,
p < 0.05) compared to the VAS scores for the calibration, 5 min, and 10 min (
Figure 3). This means that when testing for sensitivity in the tooth nerve, all patients reported more intense or severe pain (after thermal stimulation with EndoFrost) compared to the pain reported at the time of calibration or after receiving anesthesia (at 5 and 10 min).
Anesthesia success was noted in six patients for the first molar and in four patients for the second molar (
Table 1). No statistical difference (Fisher’s test,
p > 0.05) was found between first and second molars on the same or opposite sides of the mandible. The overall success rate of articaine anesthesia for mandibular molars was 36.55%, accounting for approximately 37% of the cases (see
Table 1). This was calculated by averaging the success rates for each tooth position.
No significant relationship was observed (Mann–Whitney test, Z-test,
p > 0.05) between the measurements of cortical bone thickness and the distance from the roots to the cortical bone with the administration of articaine (
Figure 4). As shown in
Figure 4, there was greater variation in the thickness and distance in successful cases. Specifically, the successful cases were performed in thicker cortical bones and at greater distances compared to the unsuccessful cases in the articaine group.
No statistical difference was observed for the buccal cortical bone thicknesses in the mesial/distal apices (ANOVA one-way—
p < 0.05). When compared to the first, the second molar showed thicker buccal cortical bone; however, the cortical bone thickness regarding both the first and second molars had no influence on the anesthetic efficacy (ANOVA one-way and Fisher’s test LSD:
p < 0.05;
Figure 5).
No statistical difference (ANOVA one-way:
p > 0.05) was observed for the distances between the mesial/distal apices and the buccal cortical bone, considering the first and second molars separately. These distances did not statistically influence the success and failure rates. When compared to the first, the second molars showed a greater distance between the mesial/distal apices and the cortical bone, considering the apices separately (ANOVA one-way and Fisher’s test LSD:
p < 0.05;
Figure 6).
The distances recorded between the second molar and the mental foramen were greater than those recorded for the first molar, considering both anesthetic success and failure (unpaired t-test:
p < 0.0001;
Figure 7).
4. Discussion
This study aimed to verify the influence of anatomical structures on the anesthetic efficacy of articaine in mandibular posterior infiltration. Utilizing CBCT images, the authors measured the relationship between anesthetic efficacy and mandibular structures, specifically the buccal cortical bone and the mental foramen, in relation to articaine success rates.
The null hypothesis that the distance between the apices of the mesial/distal roots and the buccal cortical bone thickness does not influence the rate of anesthesia success was confirmed. This study evaluated the efficacy of 4% articaine buccal infiltration into the buccal cortical bone thickness for anesthesia in mandibular molars with irreversible pulpitis. While we initially focused on articaine’s chemical properties, it is crucial to consider the anatomical and physiological aspects of the trigeminal nerve, particularly the buccal nerve branch of the mandibular division (V3).
Buccal infiltration, typically a supplementary technique to IANB, was shown in this study to function effectively as conduction anesthesia or a nerve block in cases of irreversible pulpitis. This is likely due to the anesthetic’s ability to reach and block the buccal nerve trunk, providing broader anesthesia [
11,
20]. This understanding impacts the interpretation of the present results, suggesting that the efficacy of articaine may be attributed not only to its chemical properties but also to its effective delivery as a nerve block. These findings highlight the importance of considering both pharmacological and anatomical factors when comparing the efficacy of different anesthetic techniques and agents.
The present study found no significant influence of anatomical structures on the anesthetic efficacy of articaine. The mental foramen likely facilitates articaine diffusion, while the cortical bone allows for bony infiltration. The formation of an intra-molecular hydrogen bond in the articaine molecule may enhance its ability to diffuse across the cortical mandibular bone and reach the tooth roots [
21]. Additionally, the thiophene ring in articaine has lower hydrophobicity than the benzene ring found in other local anesthetics. This lower hydrophobicity means that articaine can maintain an optimal balance between lipophilicity and water solubility, which may enhance tissue penetration without excessively binding to lipids [
22]. While this property does not directly enhance diffusion through cortical bone, it may contribute to articaine’s overall effectiveness in reaching target sites within the mandible by ensuring that the molecule remains sufficiently soluble for distribution in aqueous environments.
A low success rate (36.55%) was observed for mandibular infiltration involving the first and second molars when they had irreversible pulpitis. This low success rate is likely due to the inherent difficulties of achieving anesthesia with primary infiltration in mandibular molars affected by irreversible pulpitis, compared to sound teeth [
3,
5,
23,
24]. In cases of pulpitis, combining anesthetic techniques, such as primary mandibular infiltration with intra-ligamentary infiltration, has shown higher success rates [
4].
In the present study, the anesthesia assessment protocol involved a total of 10 min waiting period after the initial injection before starting the procedure. The investigators carefully chose this timeframe based on previous studies’ understanding of anesthetic mechanisms of action [
25,
26,
27,
28,
29]. If the anesthesia was not enough within this period, we gave an additional injection. This approach balances the need for giving the anesthetic enough time to work with the practical limits of clinical practice. While some studies suggest that shorter waiting periods might be enough, the protocol of this study takes into account that complete pulpal anesthesia may need more time in some cases, especially for patients with irreversible pulpitis. This 10 min window also allows for a more thorough assessment of how well the anesthetic is working, which could reduce the need for additional injections and make the overall procedure more comfortable for the patient.
Previous studies have suggested that anatomical structures may influence the anesthetic success of articaine [
6,
13,
14,
30]. Direct passage through the mental foramen has been proposed as one mechanism for achieving articaine infiltration efficacy in the mandibular posterior region, with reports showing anesthetic success in all tested teeth, including canines and first and second molars. Comparisons between buccal infiltration and lingual injection have suggested that the mental foramen may play a role in achieving pulpal anesthesia in posterior mandibular teeth [
30]. The assumption is that anesthetic diffusion through the mental foramen occurs when the injection targets the first molar, but it also appears to occur when the second molar is involved [
12].
Our results align with these findings, demonstrating that articaine can infiltrate through the cortical bone and reach the apices of second molar roots, despite their greater distance from the mental foramen. The large distance between the second molar and the mental foramen did not negatively impact the success rates of anesthesia. One possible explanation for this is the difference in study populations; previous studies evaluated sound teeth in young volunteers, while our study involved older patients with symptomatic irreversible pulpitis [
15,
30]. Future studies with larger sample sizes are necessary to explore this hypothesis further.
Anesthesia has higher success rates in teeth near the injection site, suggesting that the anesthetic solution also diffuses through the cortical bone. Some studies have reported better infiltration of the articaine solution in thicker cortical bone [
15,
30]. However, in our study, cortical bone thickness did not influence the success of articaine anesthesia, based on measurements from CBCT images.
It is interesting to note that the distance to the mental foramen was calculated to investigate its potential impact on the efficacy of local anesthesia. Previous studies have suggested that the mental foramen may play a role in the diffusion of anesthetics, thereby influencing the success of anesthesia in the mandibular posterior region [
11,
30,
31,
32]. By measuring the distance to the mental foramen, the authors aimed to determine whether proximity to this anatomical landmark affected the success rates of 4% articaine buccal infiltration and 2% lidocaine IANB. The present findings indicated that while there were significant differences in the distances to the mental foramen, these did not influence the anesthetic efficacy, aligning with the hypothesis that other factors, such as the inflammatory state of the pulp, may play a more crucial role.
In addition, foramina in the posterior region of the mandible may contribute to anesthetic diffusion [
30]. It has been observed that foramina in the buccal posterior surface of the mandible are infrequent, appearing closer to the mental foramen and the anterior aspect of the mandible. This parameter was not assessed in our study due to the difficulty of detecting foramina in CBCT images.
Given the high penetration ability of articaine, the macrorelief of the cortical plate, including the presence of nutrient holes on the surface at the target anesthesia points, should be considered. These anatomical features can potentially facilitate the diffusion of articaine, enhancing its efficacy. Future studies should focus on these aspects to provide a more comprehensive understanding of the factors influencing anesthetic success.
The concentration of anesthetic solution is not necessarily a predictor of enhanced efficacy. Studies have shown that articaine, lidocaine, and prilocaine at 4% concentrations do not differ significantly regarding efficacy for mandibular infiltration [
33,
34]. In vitro studies demonstrated that 2% and 4% articaine had greater efficacy in depressing the compound action potential of nerve fibers compared to 2% and 4% lidocaine [
33,
34].
Unexpectedly, our study found no significant correlation between cortical bone thickness and anesthetic efficacy. This finding contradicts previous studies and warrants further investigation [
32,
35,
36]. Other factors, such as the inflammatory state of the pulp in cases of irreversible pulpitis, may play a more significant role in determining anesthetic success than previously thought.
In this study, articaine was found to be effective as an anesthetic agent, providing some level of anesthesia in patients. However, the overall success rate for achieving complete pulpal anesthesia in mandibular molars with irreversible pulpitis was only 36.55%. It is important to distinguish between effectiveness and success. Effectiveness refers to articaine’s ability to induce numbness or partial pain relief, while success, in the context of this study, required sufficient anesthesia to allow for the complete performance of endodontic procedures without causing pain to the patient. The low success rate highlights the additional difficulties (e.g., inflammation, anxiety) that can complicate the achievement of complete anesthesia. This underscores the necessity for supplementary anesthetic techniques to improve patient outcomes in such cases.
4.1. Clinical Implications
The findings of this study have several important clinical implications. First, the low success rate (36.55%) for mandibular infiltration in cases of irreversible pulpitis underscores the need for dentists to be prepared with supplementary anesthetic techniques. Second, the lack of influence of anatomical structures on anesthetic efficacy suggests that clinicians may not need to alter their technique based on variations in cortical bone thickness or distance from the mental foramen. However, individual patient factors may still play a role in anesthetic success.
4.2. Limitations and Future Directions
While our study provides valuable insights, it has several limitations that should be addressed in future research. The small sample size limits the generalizability of our findings. Future studies should aim for larger, more diverse patient populations. Additionally, the difficulty in detecting small foramina on CBCT images means we may have missed potential routes of anesthetic diffusion. The use of more advanced imaging techniques could potentially overcome this limitation.
Another limitation is that we did not evaluate the ratio of cortical bone to spongy (cancellous) bone in relation to anesthetic efficacy. This ratio could potentially influence anesthetic diffusion and effectiveness. Future studies using more advanced imaging techniques that can better differentiate and measure both cortical and cancellous bone structures in relation to anesthetic outcomes would be valuable.
Furthermore, the anxiety levels of participants were not assessed or controlled prior to anesthesia, which may have impacted on the effectiveness of the employed techniques. Future research should consider measuring and controlling for patient anxiety to determine its potential role in anesthetic success.
In addition, the researchers chose to compare 4% articaine buccal infiltration with 2% lidocaine IANB due to their widespread use and distinct pharmacological profiles. The unique chemical properties of articaine, especially its ability to penetrate dense cortical bone, indicated potential differences in efficacy worth investigating. Our primary goal was to provide a clear evaluation of the efficacy of articaine buccal infiltration. Although including additional comparison groups (e.g., IANB with articaine, buccal infiltration with lidocaine, or varying age groups such as older versus younger participants) could yield further insights, this initial study focused on the most clinically relevant and widely utilized methods. Future research can expand upon these findings to explore broader comparisons and demographic variations.
The present study focused on patients with irreversible pulpitis, which may have influenced the anesthetic efficacy. Future research could compare anesthetic success rates between patients with and without pulpitis to better understand the impact of inflammation on local anesthesia.