Effects of Intracanal Cryotherapy on Biomarkers and Postoperative Pain in Apical Periodontitis

This randomized controlled clinical study will evaluate the effects of intracanal cryotherapy during root canal treatment in patients with asymptomatic apical periodontitis. The study will investigate whether the temperature of the final irrigation solution influences the biological inflammatory response and postoperative pain. Participants will be randomly assigned to one of three groups according to the temperature of distilled water used for final root canal irrigation: 2-4°C, 8-10°C, or 22-24°C. Periapical tissue fluid samples will be collected before and after the intervention and analyzed for inflammatory and tissue-response biomarkers, including IL-1β, TNF-α, RANKL/OPG, PGE2, TGF-β, and MMP-9. Postoperative pain and analgesic use will also be recorded during the first 7 days after treatment. The study aims to determine whether intracanal cryotherapy can reduce the inflammatory response and postoperative pain associated with root canal treatment and whether these effects vary according to the temperature of the irrigation solution.

Inclusion Criteria: * Age between 18 and 65 years. * Presence of a posterior tooth indicated for primary endodontic treatment (excluding retreatment cases). * Diagnosis of apical periodontitis, meeting the following criteria: * Necrotic pulp based on pulp vitality testing (negative cold test and/or electrical pulp test \[EPT\]). * Periapical Index (PAI) ≥3 on periapical radiography or presence of periapical radiolucency on cone-beam computed tomography (CBCT). * Asymptomatic or mildly symptomatic apical periodontitis (excluding cases of severe acute apical periodontitis). * Periodontal status meeting the following criteria: * Probing depth ≤3 mm. * Clinical attachment loss ≤2 mm. * No periodontal pockets with bleeding on probing. * The tooth to be treated must be suitable for isolation and sample collection. * Participants must be able to understand the study procedures and provide informed consent. Exclusion Criteria: * Use of antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), or -corticosteroids within the previous 3 months. * Presence of a systemic inflammatory or autoimmune disease. * Diabetes (glycated hemoglobin \[HbA1c\] ≥6.5%) or uncontrolled metabolic disease. * History of immunodeficiency or immunosuppressive therapy. * Pregnancy or breastfeeding. * Active smoking. * History of acute infection, febrile illness, or COVID-19 within the previous 3 -months. * Retreatment cases. * Presence of a fistula/sinus tract. * Periodontal probing depth \>3 mm. * Tooth mobility ≥ Grade II.