Endodontic post- operative pain is a common concern following root canal treatment, and it can significantly impact the patient's quality of life. Various strategies have been implemented to minimize or alleviate post- operative pain, including the use of non-steroidal anti- inflammatory drugs (NSAIDs), opioids, and local anesthetics. Recently, cryotherapy has emerged as a potential effect on reducing post-operative pain in various medical fields, including dentistry. It involves the use of cold temperatures to induce therapeutic effects. The application of cryotherapy in dentistry has shown promising results in reducing pain, inflammation, and swelling after oral surgical procedures. However, its efficacy in endodontics have not been extensively explored. One aspect of interest is the effect of cryotherapy on endodontic post-operative pain and its potential impact on the level of substance P. Substance P is a neuropeptide involved in pain transmission, and its release is associated with the perception of pain. By modulating the release or activity of substance P, cryotherapy could potentially influence the level of pain experienced by patients following endodontic procedures.