Patients experiencing a failed primary IANB shall be enrolled in the study. The initial failure will be defined as pain (score more than 54 on Heft Parker Visual Analog Scale (VAS) during access cavity preparation or at the root canal instrumentation stage. The primary outcome (endpoint) will be defined as "success or failure, " indicating the ability to undertake pulp access and canal instrumentation with no or mild pain. The secondary outcome will be the evaluation of heart rate after supplementary intraligamentary injections.

A tentative sample size calculation has been performed using data from a previous study, keeping the α level type I error at 0.05 for a single-tailed test and β level type II error at 0.20.19 The analysis indicated that a sample size of 35 subjects would give 80% power to detect a 30% difference in the success rates of the two different supplemental intraligamentary injections. For heart rate analysis, it has been calculated that a minimum of 23 patients per group shall be required to detect a difference of 10 beats per minute (with a baseline heart rate of 72 beats per minute).

The treatment procedure and the use of pain scales will be explained to the patients. A combined VAS, the Heft-Parker scale (HP VAS), will be used in the present study.

All patients will receive a primary IANB injection using 1.8 mL of 2% lidocaine with 1: 80 000 epinephrine using a direct Halsted approach. The needle will be inserted until bony resistance will be felt. After reaching the target area, aspiration will be performed, and the solution will be deposited over a period of 60 seconds. After 10 minutes, the patients will be asked about lip numbness. Patients without profound lip numbness will be excluded from the study since the block will be considered 'missed'. A conventional access opening will be initiated after isolation with a rubber dam. Patients will be instructed to raise their hands if any pain will be felt during the procedure. In case of pain during treatment, the procedure will be stopped, and the patients will be asked to rate the pain on the HP VAS. The patients with failed primary IANB will receive supplementary intraligamentary injections of either 2% lidocaine with 1:80 000 epinephrine or 2% lidocaine with 1:80 000 epinephrine plus tramadol hydrochloride (50 mg, 1:1 v/v ratio) or tramadol hydrochloride (25mg/mL). The cartridges will be masked with an opaque tape and coded with an alpha-numeric code. The code will be broken only after the completion of the study. The patients will be randomly allocated to three treatment groups (n=105, 35 patients per group) with the help of an online random generator. The rubber dam will be removed and the injection site will be cleaned with an antiseptic solution. The resting heart rate will be monitored with a finger pulse oximeter by a faculty member. The first group will receive intraligamentary injections of 2% lidocaine with 1: 80 000 epinephrine. The injections will be administered using a pressure-type syringe (Osung Deosy, Pearland, Tx, USA) and 30 gauge short needles (Septojet needles, Septodont). The second group will receive intraligamentary injections of 2% lidocaine with 1:80 000 epinephrine plus tramadol hydrochloride (50 mg, 1:1 v/v ratio). The third group shall receive intraligamentary injections of tramadol hydrochloride (25mg/ mL). A total of 1.2 mL of anaesthetic solution will be deposited. The heart rate will be measured at 15-second intervals till 5 minutes after intraligamentary injections. Success will be again defined as no pain or faint/weak/mild pain during endodontic access preparation and instrumentation.

Statistical analysis: The results will be tabulated in contingency tables. The age of patients will be analyzed using the Mann-Whitney U test at P \< .05. The gender and distribution of teeth will be analyzed using 2X2 contingency tables and chi-square tests. The anaesthetic success rates will be analyzed with the Pearson chi-square test. The heart rate changes will be analyzed using a t-test.