Efficacy of preoperative ibuprofen and meloxicam on the success rate of inferior alveolar nerve block for teeth with irreversible pulpitis

Introduction

Pain management and achieving anaesthesia are much more difficult in mandibular molar teeth with irreversible pulpitis than in teeth with normal healthy pulps¹. Despite development of the signs of anaesthesia, such as numbness of the lower lip and the tip of the tongue, many patients still experience some degree of pain while the access cavity is being prepared.

Previous studies have suggested several solutions to increase the depth of anaesthesia during root canal therapy in these teeth, including: (i) use of a higher dose of adrenaline in anaesthetics, which actually had no considerable effect in lowering the level of pain and increasing the depth of anaesthesia2., 3.; (ii) performing supplemental injections alongside inferior alveolar nerve block (IANB), which takes account of just 58% of the success rate of anaesthesia besides alveolar nerve block⁴; and (iii) administration of pain and anti-inflammatory medications 1 hour before the treatment, which has shown considerable success in increasing the depth of anaesthesia1., 5.. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) with preferential activity on the cyclooxygenase 2 (COX-2) system6., 7.. Therefore, it has less effect on the gastrointestinal tract compared with other types of NSAIDs. Meloxicam is also effective in the treatment of osteoarthritis and rheumatoid arthritis8., 9.; nevertheless, its level of efficacy in reducing the pain during and after endodontic treatment has not been evaluated.

The purpose of this prospective randomised double-blind clinical trial was to compare the anaesthetic efficacy in first molar teeth with symptomatic irreversible pulpitis using two techniques – electric pulp testing (EPT) and cavity testing – after a block injection with or without premedication.

Materials and Methods

Ninety-two patients in need of endodontic therapy, in the department of Endodontics at Shahid Beheshti University, volunteered to participate in this study. This study was approved by the Ethics Committee of Shahid Beheshti University of Medical Sciences with the registry ID of IRCT2015071423207N1. Written informed consent was obtained from all participants after complete explanation of the purpose, nature and probable risks and discomforts of this procedure. This study was conducted in full accordance with the World Medical Association Declaration of Helsinki.

The subjects included in this study were completely healthy with no systemic diseases. Also, the patients had not taken any kind of medication, within a period of 8 hours before treatment, that could interfere with the medications used in this study. Exclusion criteria were casting restorations, previous endodontic therapies, severe periodontal diseases and periapical radiolucencies; pregnancy or breastfeeding; and contraindications to the drugs used in this study. The patients included had a mandibular first molar with a history of spontaneous pain and a prolonged response (of more than 10 seconds) of mild to severe pain to cold testing.

A pharmacist divided 69 capsules of the same colour and size (00 size) into three groups: meloxicam; ibuprofen; and placebo. Meloxicam capsules were filled with 7.5 mg of meloxicam; ibuprofen capsules were filled with 600 mg of ibuprofen; and placebo capsules were filled with starch powder. Then, 6-digit random numbers were assigned to each capsule, in order to ensure that neither the clinician nor the patients were aware of the type of medication taken. The subjects were then divided into four groups of 23 patients each. In order to randomise the patients, they were asked to choose one envelope in which a number from one to four was written on a piece of paper. The first group [the no-premedication group (NOPg)] received no premedication; the second group [the meloxicam group (MELg)] received 7.5 mg of meloxicam (Samisaz Pharmaceutical Co., Tehran, Iran); the third group [the ibuprofen group (IBUg)] received 600 mg of ibuprofen (Aria Pharmaceutical Co., Tehran, Iran); and the fourth group [the placebo group (PLAg)] received placebo (starch powder).

Before taking the capsules, the patients were asked to rate their pain using the Heft–Parker visual analogue scale (VAS)¹⁰. This scale extends from 0 to 170 mm and consists of mild, moderate and severe levels of pain. Absence of pain is defined as 0 mm, 54 mm or less is an indicator of mild pain, 54–144 mm corresponds to moderate pain and higher than 144 mm is considered as severe pain. Afterwards, the teeth were dried and isolated by cotton rolls. Then, small amounts of toothpaste were placed between the teeth and the head of the electric pulp tester probe head (The Element Diagnostic Unit; SybronEndo, Glendora, CA, USA). The head of the pulp tester was placed on the upper level of the cervical third of the buccal surface of the teeth, to avoid false-positive responses11., 12., 13.. The patients were asked to raise their hands when they felt any heat, tingling or pain. With the patients' signal, the head of the probe was detached from their teeth and the values of EPT (0–80) were recorded on data sheets. In order to avoid false responses, the tests were performed twice¹⁴, and two vital teeth adjacent to the first molar in the same quadrant were used as the control15., 16..

One hour after administration of the capsules, all patients received injection of standard IANB with 1.8 ml of 2% lidocaine and a 1:100,000 dilution of adrenaline (Daroupakhsh, Tehran, Iran) by the same clinician. Numbness of the lower lip and tip of the tongue developed 15 minutes after receiving IANB. If the numbness of the lower lip had not appeared, the patient was excluded from the study. Before preparing the access cavity, the teeth were tested by EPT once more and the results were recorded. Afterwards, the clinician prepared the access cavity and patients were asked to rate their level of pain using the Heft–Parker VAS in the middle of the procedure, in case of any pain sensation. IANB was considered successful if there was no, or only mild, pain (VAS recordings) while preparing the access cavity or during initial instrumentation¹⁷ and no response to the EPT.

The paired T-test was used to analyse the findings from EPT and Heft–Parker VAS in each group, before and after intervention. Also, data were analysed using the repeated-measures ANOVA for comparison of the groups as a whole, and the Tukey honestly significant difference (HSD) test was used to compare results between groups.

Results

Ninety-two patients in need of endodontic therapy participated in this clinical trial. Profound lip numbness was recorded for all the patients following the first injection and none was excluded from the study. The average age of the participants and their age distribution are shown in Table 1. No significant differences between groups were found for gender and average age (P > 0.05). In order to confirm that the groups were balanced, one-way ANOVA was performed and no significant differences were found between the results of EPT and Heft–Parker VAS before the intervention.

Table 1.

Sample distribution

Groups	Sample size	Number (%) of male participants	Number (%) of female participants	Average age of participants(years)	SD of age(years)
NOPg	23	11 (47.8)	12 (52.2)	29.26	5.93
MELg	23	10 (43.5)	13 (56.5)	32.78	9.55
IBUg	23	10 (43.5)	13 (56.5)	31.70	8.04
PLAg	23	13 (56.5)	10 (43.5)	32.22	8.87

IBUg, ibuprofen group; MELg, meloxicam group; NOPg, no-premedication group; PLAg, placebo group; SD, standard deviation.

After the intervention, the EPT values were significantly higher in all groups. These groups also showed significantly lower responses to the Heft–Parker VAS (Table 2). Regarding the repeated-measures ANOVA, the EPT value was significantly higher in MELg and IBUg, compared with NOPg and PLAg, before and after intervention (P < 0.001). The increase in the EPT value was not significant in NOPg compared with PLAg (P > 0.999) or in MELg compared with IBUg (P = 0.930). The Heft–Parker VAS values were also significantly lower in MELg and IBUg compared with the NOPg and PLAg (P < 0.001), but there were no statistically significant differences between the reductions in Heft–Parker VAS values of MELg versus IBUg (P = 0.750), and of NOPg versus PLAg (P = 0.914).

Table 2.

Patients' response to electrical pulp testing (EPT) and Heft–Parker visual analogue scale (VAS) in the four study groups

Groups	EPT		VAS
	Before intervention(mean ± SD)	After intervention(mean ± SD)	Before intervention(mean ± SD)	After intervention(mean ± SD)
NOPg	29 ± 10	70.52 ± 9.3	106.5 ± 40	81.7 ± 50
MELg	20.91 ± 6.5	77.78 ± 4	99.1 ± 33	28.3 ± 40
IBUg	19.61 ± 7.3	78.43 ± 3.7	102.2 ± 30	20 ± 30
PLAg	29.26 ± 10	70.48 ± 11	94.8 ± 34	62.6 ± 53

IBUg, ibuprofen group; MELg, meloxicam group; NOPg, no-premedication group; PLAg, placebo group; SD, standard deviation.

According to the criteria of this study for considering an IANB injection successful, the overall success rates of IANB for the NOPg, MELg, IBUg and PLAg were 21.7%, 65.2%, 82.6% and 34.8%, respectively, considering the Heft–Parker VAS values. According to EPT values, the IANB success rates were 21.7% for the NOPg, 73.9% for the MELg, 78.3% for the IBUg and 34.8% for the PLAg (Tables 3 and 4).

Table 3.

Comparison of success rates in each group according to Heft–Parker visual analogue scale (VAS) values

Groups	Success rate of anaesthesia(%)	Sample size(n)	Responses with no or mild pain(n)	Responses with moderate pain(n)	Responses with severe pain(n)
NOPg	21.7	23	5	13	5
MELg	65.2	23	16	7	0
IBUg	82.6	23	20	3	0
PLAg	34.8	23	8	11	4

IBUg, ibuprofen group; MELg, meloxicam group; NOPg, no-premedication group; PLAg, placebo group.

Table 4.

Comparison of success rates in each group according to electrical pulp testing (EPT) values

Groups	Success rate of anaesthesia (%)	Sample size(n)	No response to EPT on 80(n)
NOPg	21.7	23	5
MELg	73.9	23	17
IBUg	78.3	23	18
PLAg	34.8	23	8

IBUg, ibuprofen group; MELg, meloxicam group; NOPg, no-premedication group; PLAg, placebo group.

The success rate of IANB after intervention and after using the EPT test showed no significant differences between the NOPg compared with the PLAg (P = 0.978), and the MELg compared with the IBUg (P > 0.999). Nevertheless, compared with the PLAg and the NOPg, IBUg and MELg had higher success rates (P < 0.001).

Discussion

Irreversible pulpitis can be a major challenge in achieving anaesthesia because the inflammatory mediators have various effects on sensory nerve endings. Even when a proper technique is employed, conventional methods of anaesthesia fail in 30–45% of patients with an inflamed tooth¹⁸. In some cases, despite achieving the desirable degree of anaesthesia, patients still experience pain during preparation of the access cavity. The reason is that not all of the pulpal sensory nerves are blocked. A useful tool in these cases can be the use of EPT testing before preparing the access cavity.

The failure of IANB to obtain satisfactory analgesia in mandibular molars is associated with several factors. One could be anatomical reasons, such as mylohyoid nerve accessory innervation to mandibular molars. Lingual, buccal and inferior dental nerves, cutaneous coli and the superior and inferior laryngeal branches of the vagus nerve might also innervate the teeth¹⁸. Another factor could be related to tetrodotoxin-resistant ionic channels (TTX-r) and failure to achieve their full blockade. The persistent TTX-r currents could be increased by prostaglandin E₂ (PGE2), which is an important inflammatory mediator elevated in symptomatic pulpitis. The main mechanism of NSAIDs is the attenuation of PGE2 production by inhibition of cyclooxygenases. Thus, it is hypothesised that premedication with NSAIDs will potentiate the efficacy of the anaesthetic solution¹⁹. Accordingly, the present study was conducted to evaluate the efficacy of meloxicam and ibuprofen, used as premedication, on the success rate of inferior alveolar nerve block.

The success rate of anaesthesia for the MELg and the IBUg were, respectively, recorded as 73.9% and 78.3%, according to EPT, and 65.2% and 82.6% considering the Heft–Parker VAS values. For the NOPg and the PLAg, these values were, respectively, measured as 21.7% and 34.8% by EPT, and 21.7% and 34.8% using the Heft–Parker VAS. These results indicate that a single nerve block injection in teeth with irreversible pulpitis cannot provide profound anaesthesia for endodontic treatment; hence, supplementary actions are needed.

In a similar study by Paul et al.¹⁷ the effect of preoperative aceclofenac on the success of inferior alveolar nerve block in patients with irreversible pulpitis was evaluated using the Heft–Parker VAS. The results showed that the success rate for the IAN block was significantly higher with aceclofenac (65%) in comparison with placebo (35%). In the present study, the depth of anaesthesia was increased by premedication with ibuprofen and meloxicam. Moreover, not only was the level of patients' pain evaluated using the Heft–Parker VAS while the access cavity was being prepared, but the success of IANB was also measured, before starting the treatment, by EPT. The failure rate of IANB in teeth with irreversible pulpitis after receiving the injection was also recorded.

The results of this study are in agreement with those of Modaresi and Dianat⁵ who have shown that premedication with ketorolac an hour before treatment could increase the depth of anaesthesia in inflamed teeth.

There is numerous research in the field of analgesic premedication, specially ibuprofen, on the success of IANB. Parirokh et al.¹, in a study to determine the effect of premedication with ibuprofen and indomethacin on the success of inferior alveolar nerve block for teeth with irreversible pulpitis, using Heft–Parker VAS, found that the administration of 600 mg of ibuprofen and 75 mg of indomethacin, 1 hour before local anaesthesia, was significantly better than placebo. However, there was no difference between ibuprofen and indomethacin. The results of the study carried out by Parirokh are in agreement with the results of the present study.

Modaresi et al.²⁰ evaluated the effect of premedication therapy with acetaminophen+codeine or ibuprofen using EPT to record sensitivity at baseline and after drug administration and anaesthesia injection. Significantly lower tooth-sensitivity levels (TSLs) were observed after intervention in the acetaminophen+codeine and ibuprofen groups in comparison with the placebo group. In this study, the level of pain was evaluated only after receiving the injection, whereas in the present study the level of pain was estimated two methods – EPT and Heft–Parker VAS – not only before premedication and IANB injection, but also after receiving the premedication and injection and while preparing the access cavity. Nonetheless, the results of this study agree with those of Modaresi et al.²⁰

Noguera-Gonzalez et al. studied 50 patients with symptomatic irreversible pulpitis and reported that preoperative administration of 600 mg of ibuprofen significantly improved the efficacy of IANB. Although they used mepivacaine as the anaesthetic solution, the results of this study are comparable to those of Noguera-Gonzalez et al.¹⁹.

A systematic review on the effect and safety of pre-emptive oral NSAIDs for the success of IANB in irreversible pulpitis treatment²¹ suggests that pre-emptive oral NSAIDs have a positive effect, are safe and increase the success rate of IANB; however, further research is needed.

In contrast to the previously mentioned studies, several studies have reported that premedication has no significant effect on the success rate of IANB in patients with irreversible pulpitis. The effect of a combination of preoperative ibuprofen+acetaminophen on the success of IANB in patients with irreversible pulpitis was evaluated by Simpson et al.²² It was shown that for mandibular posterior teeth, a combination dose of 800 mg ibuprofen and 1,000 mg of acetaminophen, given 45 minutes before administration of the IANB, did not result in a statistically significant increase in anaesthetic success. This disparity in results may be because of differences in degree and duration of pulpal inflammation in study participants.

The effect of preoperative ibuprofen on the success of the inferior alveolar nerve block in patients with irreversible pulpitis was carried out by Oleson et al.²³ in which a dose of 800 mg of ibuprofen was given 45 minutes before administration of the IANB, but their result did not show any significant increase in the success of IANB in patients with irreversible pulpitis.

Aggrawal et al.²⁴ studied the effect of ibuprofen and ketorolac and found that preoperative administration of ibuprofen or ketorolac has no significant effect on the success rate of IANB in patients with irreversible pulpitis. The disparity between the results of the study by Aggrawal et al.²⁴ and those of the present study might be a result of the nature of subjective tests such as the Heft–Parker VAS. This is the reason why EPT was used in this study as an objective test, along with the Heft–Parker VAS.

The present study applied two NSAIDs: ibuprofen and meloxicam. Ibuprofen is a nonselective drug that inhibits the cyclooxygenase enzyme that inhibits both COX1 and COX2 isoforms. The analgesic effect of this medication occurs through inhibiting the effect of COX2, while its inhibitory impact on COX1 leads to complications within the gastrointestinal system. Meloxicam is a relatively selective COX2 inhibitor and has a less disturbing effect on the gastrointestinal system compared with other NSAIDs. Although elevated risk of myocardial infarction and stroke associated with use of selective COX2 inhibitors, such as rofecoxib and celecoxib, has been reported, meloxicam has a more desirable cardiovascular safety profile25., 26., 27..

During the clinical trial of this study, the analgesic effect of 7.5 mg of meloxicam was evaluated 1 hour before endodontic treatment of mandibular molars with irreversible pulpitis, which has so far not been studied. Meloxicam was confirmed to be effective in reducing pain in patients with inflamed teeth. However, further clinical studies are suggested to evaluate the efficiency of different dosages of meloxicam.

In conclusion, the results of the current study support premedication with NSAIDs, 1 hour before the administration of the IANB, in patients with irreversible pulpitis. However, further clinical studies are required to clarify the potential of other analgesic regimens in pain control and successful anaesthesia during endodontic treatment.

Acknowledgements

The authors would like to acknowledge the Research Deputy, Dental School, Shahid Beheshti University of Medical Sciences for the financial support of this research. The authors deny any conflicts of interest related to this study.