Acute inflammation of the dental pulp: irreversible pulpitis

Acute inflammation of the dental pulp (Figure 1) is a biological response to harmful stimuli such as caries, trauma, bacterial infections, or chemical exposure. It involves the neural and vascular tissue within the pulp [18]. The dental pulp, made up of nerves, blood vessels, and connective tissue, is enclosed in the pulp chamber within the tooth. When the pulp is damaged, an inflammatory process occurs, aiming to limit injury and restore homeostasis; if untreated, this can lead to permanent tissue damage and more serious complications [19].

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Figure 1. Molar with irreversible pulpitis.

During acute inflammation, chemical mediators such as prostaglandins, cytokines, and chemokines are released by the damaged tissues. These mediators cause various local effects, including vasodilation, increased capillary permeability, and hemoconcentration, resulting in swelling and heightened nerve sensitivity [20]. Pain is one of the main symptoms of acute pulp inflammation. It is often described as intense, throbbing, and continuous, and may persist even after the removal of the stimulus due to internal pressure within the tooth that cannot be released because of the rigidity of the dental walls [21].

The increased nerve sensitization makes patients particularly reactive to stimuli such as heat, cold, or pressure—and sometimes even spontaneous pain—which is often unresponsive to common painkillers. At this stage, the only effective treatment is endodontic therapy (root canal treatment) or tooth extraction [22, 23].

Inferior alveolar nerve anesthesia: techniques and effectiveness

Inferior alveolar nerve anesthesia is one of the most common and effective techniques for pain control during dental procedures involving lower teeth, especially in surgical or endodontic treatments [24–26]. The inferior alveolar nerve (Figure 2) provides sensory innervation to most mandibular teeth, the gingiva, and the surrounding bone. It can be anesthetized through a nerve block technique, in which a local anesthetic is injected near the nerve trunk close to the mandibular foramen.

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Figure 2. Course of the trigeminal nerve.

Despite its high success rate, nerve block anesthesia can present challenges, and the techniques may vary depending on individual anatomical and clinical factors [27, 28].

The traditional IANB is the most widely used technique in dentistry. It involves injecting the anesthetic into the retromolar area near the mandibular foramen, which is the entry point of the inferior alveolar nerve into the mandible [24]. The injection is administered where the nerve is most accessible along the mandibular bone; however, its clinical efficacy can vary significantly depending on the anesthetic protocol and the inflammatory state of the pulp [1].

The advantages of this technique include its ease of execution and its effectiveness in anesthetizing the entire mandibular side, including teeth, gingiva, tongue, and floor of the mouth. However, its effect may be reduced in the presence of local infections or inflammation that alter drug responsiveness, or in cases of anatomical variations such as unusual foramen positions or fibrous tissue presence [1]. The block may also be incomplete in certain areas of the mandible, such as premolars or the incisor region.

Although the traditional technique is most commonly used, variants such as the Gow-Gates and Akinosi techniques offer valid alternatives, especially in cases of failed conventional anesthesia or anatomical difficulties [22].

The Gow-Gates technique aims to block not only the inferior alveolar nerve but also other nerves involved in mandibular treatment, such as the lingual and buccal nerves. In this method, the injection is made higher than in the traditional technique, at the neck of the mandibular condyle in the pterygomandibular region [22].

An alternative to nerve block anesthesia is the intraligamentary or intrapulpal injection technique, used in cases where the initial block fails. In these methods, the anesthetic is injected directly into the pulp chamber or periodontal space to achieve a rapid, localized block [29].

Anti-inflammatory drugs for pain management

The use of anti-inflammatory drugs as premedication in cases of IP primarily aims to reduce acute inflammation of the dental pulp and improve pain control during dental procedures.

NSAIDs such as ibuprofen and diclofenac are widely used for their anti-inflammatory, analgesic, and antipyretic effects. These drugs work by inhibiting cyclooxygenase enzymes (COX-1 and COX-2), which are involved in the production of prostaglandins—chemical mediators that play a crucial role in the inflammatory process and in pain sensitization [30, 31].

By reducing prostaglandin production, NSAIDs not only alleviate the pain associated with pulpitis but also help limit vasodilation and tissue edema, thereby improving perfusion and the access of anesthetic drugs to the target site [32]. This anti-inflammatory effect can significantly enhance the effectiveness of IANB, as acute inflammation can reduce anesthetic diffusion and hinder its analgesic action [33–35].

Therefore, taking NSAIDs before the anesthetic procedure can enhance the nerve block, promoting a more prolonged and complete response to local anesthesia and reducing the risk of anesthetic failure in patients with IP [36]. This integrated approach improves patient comfort, decreases the need for high anesthetic doses, and contributes to more effective pain management during and after dental treatment [37–40].

Protocol and registration

This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under the ID: CRD420251062710.

Search processing

We searched databases such as Scopus, Web of Science (WoS), and PubMed using the keywords “anti-inflammatory, alveolar nerve block, and pulpitis” to find studies related to this topic. Only English-language articles were considered, and the search was limited to the past ten years (2014–2024). In addition to the main electronic databases, a supplementary search was conducted in the international clinical trial registry ClinicalTrials.gov (https://clinicaltrials.gov/) to identify ongoing, unpublished, or registered studies that might meet the inclusion criteria of this systematic review. At the time of the search, no registered clinical trials were found that met the eligibility criteria. This step was undertaken to ensure the comprehensiveness of the review and to minimize the risk of publication bias.

Inclusion and exclusion criteria

Articles that met the following inclusion criteria were double-blindly selected by the reviewers: (1) studies involving human participants; (2) clinical research, case studies, or randomized controlled trials (RCTs), examining the effectiveness of AIT in combination with truncular anaesthesia of the alveolar nerve in patients with IP. Reviews and meta-analyses, animal model studies, and in vitro experiments were excluded. Studies in patients with a diagnosis other than IP, studies not examining truncular anaesthesia, studies with inappropriate methodologies, or not reporting measurable results were excluded.

Table 1 shows the components of the PICOS criteria (population, intervention, comparison, outcome, study design) as well as their use in the evaluation.

Data processing

As part of the screening process, which involved reviewing the titles and abstracts of the articles selected in the previous identification step, the full texts of the included publications were examined after excluding those that did not address the topics under investigation.

Quality assessment

Using ROBINS, a tool designed to assess the risk of bias in the results of non-randomized studies comparing the health effects of two or more interventions, three reviewers—AS, LPZ, FED—evaluated the quality of the included publications. Each of the seven assessed criteria was assigned a level of bias (Table 3). In addition, for all RCTs, the risk of bias was assessed using the Cochrane Risk of Bias 2.0 (ROB 2.0) tool to ensure a comprehensive and appropriate evaluation of study quality based on study design (Table 4).

A GRADE assessment was conducted to evaluate the overall certainty of the evidence for the main outcomes analyzed in this review. The outcome “success rate of IANB” following preoperative administration of NSAIDs or corticosteroids was supported by RCTs with mostly low to moderate risk of bias. However, inconsistency across drug types, dosages, and outcome definitions introduced some imprecision. Based on these factors, the certainty of evidence for this outcome was rated as moderate. Similarly, evidence for the reduction in postoperative pain after premedication with anti-inflammatory drugs was also judged to have moderate to high certainty. These ratings suggest that current findings are likely to reflect true effects, although further high-quality trials may impact future estimates.

Full details of the GRADE evaluation are presented in Table 5.

To facilitate visual comparison across studies, a summary chart was developed illustrating the reported IANB success rates for each pharmacological agent. Figure 4 displays the relative effectiveness of NSAIDs and corticosteroids as preoperative medications compared to placebo. Although a meta-analysis was not feasible due to methodological heterogeneity, this visual summary highlights consistent improvements in anesthetic success with anti-inflammatory premedication.

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Figure 4. Comparative success rates (%) of IANB following premedication with different anti-inflammatory agents across the included randomized controlled trials. The chart illustrates a consistent advantage of NSAIDs and corticosteroids over placebo. IANB: inferior alveolar nerve block; NSAIDs: non-steroidal anti-inflammatory drugs.

Effectiveness of NSAIDs

The most studied drug is undoubtedly ibuprofen. In several studies, including those by de Oliveira et al. [39], Bidar et al. [41], and Riaz et al. [19], preoperative administration of ibuprofen significantly improved the success of IANB. De Oliveira compared 600 mg ibuprofen, an ibuprofen-arginine formulation, and a placebo, reporting anesthetic success rates of 78% in the ibuprofen-arginine group, 62% with pure ibuprofen, and only 34% in the control group. Another study by Saha et al. [16] concluded that oral premedication with 10 mg Ketorolac significantly increases the likelihood of achieving effective anesthesia in patients with symptomatic irreversible pulpitis.

Ibuprofen combined with other analgesics has also shown promising results. Elnaghy et al. [36] compared tramadol, ibuprofen, and a combination of ibuprofen/acetaminophen, finding a success rate of 62% in patients premedicated with 100 mg of tramadol, indicating a significant improvement in anesthetic efficacy. Conversely, no statistically significant differences were observed among the other groups. These data suggest that the ibuprofen/acetaminophen combination may offer slightly greater efficacy, possibly due to the complementary mechanisms of action. Other studies have evaluated alternative NSAIDs. Kumar et al. [42] compared 650 mg paracetamol and 10 mg ketorolac, reporting success rates of 43% for ketorolac and 33% for paracetamol, versus 29% in the control group. Elnaghy et al. [43] also included meloxicam (7.5 mg), ketorolac (10 mg), ibuprofen (600 mg), and dexamethasone (0.5 mg) in a direct comparison. In this study, all treatment groups achieved higher results than the control, with anesthetic success ranging from 52% to 64%, while the placebo group showed only 32%.

Encouraging results for corticosteroids

The use of corticosteroids as premedication is receiving increasing attention. Rodrigues et al. [18] compared dexamethasone (4 mg), diclofenac potassium (50 mg), and placebo. The dexamethasone group achieved a success rate of 39.3%, higher than both the diclofenac group (21.4%) and the control group (3.6%). Similarly, Hegde et al. [30] compared dexamethasone with prednisolone and placebo, reporting success rates of 60.86% and 56.52% in the treated groups, versus 21.73% in the control group. Aggarwal et al. [44] also showed that a single intraligamentary injection of 4 mg/mL dexamethasone significantly improved the effectiveness of lidocaine anesthesia, with a success rate of 73% compared to 32% in the placebo group. These results support the idea that corticosteroids, due to their potent anti-inflammatory action, may be useful in cases of acute pain and deep inflammation, such as IP.

Other pharmacological approaches

In addition to NSAIDs and corticosteroids, some studies have evaluated combinations with opioids or centrally acting analgesics. Fullmer et al. [33] tested the effect of acetaminophen/hydrocodone (1,000 mg/10 mg), reporting a success rate of 32% compared with 28% in the placebo group, with the difference between the two groups not being statistically significant.

Nivedha et al. [45] studied the effectiveness of 10 mg ketorolac combined with different local anesthetics and irrigants. Although the benefit was more evident in postoperative pain control than in the intraoperative phase, IANB effectiveness also improved, particularly when ketorolac was combined with lidocaine and epinephrine.

Factors influencing premedication response

One of the most interesting aspects concerns the study by Singh et al. [10], which evaluated the effectiveness of ibuprofen premedication in patients who chew tobacco. Although the drug was effective in both groups, the success rate was slightly lower in chewing tobacco users, suggesting a potential influence of chronic nicotine consumption on anesthetic response. However, the difference was not statistically significant, but it opens avenues for future research.

Limitations of the evidence

Despite encouraging results, several limitations must be acknowledged.

First, the included studies exhibited substantial heterogeneity in terms of drug types, dosages, and timing of administration, which limited the possibility of conducting a quantitative synthesis and affected the generalizability of the findings. Furthermore, the definitions of anesthetic success varied across studies (e.g., different pain assessment scales, success thresholds, and procedural endpoints), introducing a risk of indirectness in the comparison of outcomes.

Second, some studies did not report essential statistical measures such as standard deviations or confidence intervals, or error margins for their outcomes, reducing the ability to assess internal consistency and reliability of the findings, and limiting the feasibility of conducting a meta-analysis. Only a few trials, such as that by Nivedha et al. [45], included standard deviations alongside mean pain scores; most studies did not.

Additionally, the potential for publication bias cannot be excluded, especially considering that no eligible unpublished or ongoing studies were found during the search of trial registries. Some trials lacked information on blinding or allocation concealment, potentially introducing performance or detection bias.

Lastly, the quality assessment using tools such as ROBINS revealed a variable risk of bias, underscoring the need for careful interpretation of the results.

Future high-quality RCTs with standardized methodologies and transparent statistical reporting are necessary to confirm and refine the current evidence.

Final considerations

Overall, the data clearly indicate that premedication with NSAIDs or corticosteroids (particularly NSAIDs such as ibuprofen, ketorolac, diclofenac, and piroxicam, as well as corticosteroids like dexamethasone and prednisolone) significantly improves the success of IANB in patients with symptomatic IP. Success rates in treated groups generally range between 55% and 73%, while control groups rarely exceed 40%. The choice of drug, dosage, route of administration, and the patient’s clinical condition (including behavioral factors) can influence the outcome, but the benefit of premedication is now well documented. The growing body of evidence suggests that the use of pharmacological premedication should be considered to improve intraoperative comfort and reduce the need for supplemental anesthesia.

The management of anesthesia in patients with symptomatic IP represents a significant challenge in endodontic practice, particularly due to the low efficacy of the IANB in cases of acute pulpal inflammation [39, 40, 46–48]. The reviewed data consistently demonstrate that pharmacological premedication, whether with NSAIDs or corticosteroids, can significantly improve the anesthetic success rate of the IANB in patients with symptomatic IP, reducing intraoperative pain and the need for supplemental anesthesia. Among NSAIDs, ibuprofen—especially when combined with other analgesics like acetaminophen—has proven to be one of the most effective options, showing success rates markedly higher than placebo. Other NSAIDs, such as ketorolac and meloxicam, have also shown promising results. Corticosteroids, particularly dexamethasone, have shown comparable or even superior efficacy to NSAIDs, likely due to their potent anti-inflammatory properties [44]. Although some individual factors, such as nicotine use, may slightly influence the response to premedication, the overall effect remains positive. These findings support the systematic integration of pharmacological premedication into endodontic protocols for patients with symptomatic IP, with the aim of optimizing anesthetic effectiveness and improving the patient’s clinical experience.

Further RCTs with consistent reporting of outcome variability (e.g., standard deviations and confidence intervals) are needed to enable stronger quantitative comparisons.