This study aims to improve the postoperative endodontic outcome by assessing the effect of different irrigants on postoperative endodontic pain and their anti-inflammatory effects.

Alternating application of ethylenediaminetetraacetic acid (EDTA) and sodium hypochlorite (NaOCl) is frequently recommended for removal of organic and inorganic tissues debris including the smear layer. But EDTA can cause loss of available chlorine affecting organic tissue dissolving ability of NaOCl when mixed with it. Etidronic acid is a first-generation bisphosphonate. It is a mild chelator that is compatible with NaOCl in the short term without affecting available chlorine, a concept that has been termed 'continuous chelation'. Clodronate also, was identified with improved stability in NaOCl mixtures compared with EDTA and etidronate.

Aim: Assessment of postoperative endodontic pain and matrix metalloproteinase-9 levels after sequential versus continous chelation protocols.

Methods: This study will be conducted on 75 patients having necrotic pulp with asymptomatic apical periodontitis. Patients will be randomly divided into five groups (Group 1: 2.5% NaOCl during instrumentation then sequential chelation by 17% EDTA, Group 2: 2.5% NaOCl during instrumentation then sequential chelation by 9% HEBP, Group 3: 2.5% NaOCl during instrumentation then sequential chelation by 0.26 M (7.6%) clodronate, Group 4: continuous chelation during instrumentation by 2.5% NaOCl + 9% HEBP, Group 5: continuous chelation by 2.5% NaOCl + 0.26 M (7.6%) clodronate). Postoperative pain will be assessed after 6, 12, 24, 48 hours and 7 days after the first visit using a numerical rating scale. MMP-9 levels in periapical tissues will be quantified using a commercially available ELISA kit applied on the periapical samples that will be collected after the final rinse (S1) and after one week (S2).

Inclusion Criteria:

1. Patients presenting with a single rooted tooth (maxillary anteriors and mandibular premolars) with closed apex and a single patent canal type I in Vertucci's classification (Vertucci et al., 1974)
2. Having a necrotic pulp and asymptomatic apical periodontitis (periapical lesion).
3. Periapical lesions of endodontic origin with a diameter ranging from 2 to 5mm, having a periapical index score of 4 or 5 (Orstavik, Kerekes and Eriksen, 1986)

Exclusion Criteria:

(i) Patients with pain before treatment (ii) Patients having chronic condition requiring the intake of anti-inflammatory/antibiotic drugs.

(iii) Teeth having non-restorable tooth with gross carious lesions, fractures, internal or external root resorption or cracks involving the periodontium.

(iv) Root canals in which patency for periapical fluid sampling could not be achieved.

(v) immune-compromised patients or patients with complicated systemic diseases, physical disability or psychological problems (vi) patients received antibiotic therapy within the last 3months. (vii) Teeth associated with bone expansion or with a history of endodontic treatment.

(viii) Teeth with periodontal pockets deeper than 4mm, with or without concomitant or combined endo-perio communication.

study protocol and results