MATERIALS AND METHODS This prospective randomized comparative clinical trial was conducted in the integrated clinical course in the dental school of the University of Greifswald, Germany after the approval of the local ethics committee of the medical faculty in Greifswald (No. BB 174/18) in a period from December 2018 to June 2019. The sample size calculation using "G\*power version 3.1" (Heinrich-Heine-University / Germany) was based on the following estimates: T-test for means (difference between two independent means), effect size 0.7, α error 0.05 and power (1-ß error) 0.9. It resulted in a samples size of 36 patients in each of the two groups (IANB \& ILA).

Inclusion and Exclusion Criteria The patients requiring regular dental in permanent mandibular posterior teeth under local anesthesia were recruited with an age range of 18 to 50 years. Patients were not included if they had a clinical or radiographic sign of acute abscess, pus or peri-radicular pathology. Also patients with a systemic disease requiring special considerations during their dental treatment or patients with contra-indications for any of the components of the anesthetic solution (allergy to articaine, epinephrine, and sulfite) were excluded.

Clinical Treatment and Outcome Computer-generated randomization technique was applied to allocate the participants to one of the both study groups (ILA vs. IANB). The intensity of pain as well as stress during the injection of the local anesthesia and during the dental procedure was assessed by using the Numeric Rating Scale (NRS 0-10). The anesthesia was performed by the clinical instructors of the course being dental practitioners (GDPs) or by dental students in the 4th and 5th academic year in the integrated clinical course in the dental school of the University of Greifswald and recorded as dentist or student. The distributions of different experience level of clinical instructors, dental students in 4th and 5th year were considered. For the inferior alveolar nerve block, the patient was placed comfortably in a supine position on the dental chair. The start of the anesthetic procedure was done without using topical anesthesia. The IANB injection was administered with cannulas of 38 mm in length and a gauge of 0.4 mm (Sopira Carpule, Heraeus Kulzer GmbH Hanau, Germany). The patients were anesthetized with Ultracain DS Forte 1:100.00 (Sanofi Aventis, Germany), the active ingredient being articaine in 1.7 ml ampules (1 ml equal to 40 mg articaine hydrochloride and 0.012 mg epinephrine hydrochloride, which is included as a vasoconstrictor). Once the bone was contacted, 1.5 ml of anesthetic solution was injected slowly. Subsequently the needle was detached for approximately 1 cm and an addition of 0.3-0.5 ml of local anesthetic solution was injected to anesthetize the lingual nerve.

For the intraligamentary anesthesia, three different syringe systems were used with randomized selection: Softjet syringe (Henke-Sass Wolf, Tuttlingen, Germany), Citojet syringe (Sopira, Heraeus Kulzer GmbH Hanau, Germany), Ultrajet syringe (Sanofi-Aventis, Frankfurt am Main, Germany). The patients were also placed in a supine position and the dentist administered the ILA injection without using topical anesthesia with cannulas of 12 mm in length and a gauge of 0.30 mm (Sopira Carpule, Heraeus Kulzer GmbH Hanau, Germany). Also, Ultracain DS Forte 1:100.000 (Sanofi Aventis, Germany) was used from 1.7 ml ampules. The needle was navigated through the gingival sulcus with the bevel towards the alveolar bone and away from the root surface, at an angle of 30°-40° to the long axis of the tooth and 2- 3 mm into the periodontal ligament space between root and alveolar bone. For each root, 0.2 ml of local anesthetic was injected over at least 20 seconds according to Endo et al. (2008) as well as Bender and Taubenheim (2014).