This study aims to investigate the relationship between systemic inflammatory markers and the effectiveness of inferior alveolar nerve block anesthesia in patients undergoing dental treatment. The primary focus is on the Systemic Inflammatory Index (SII) and other inflammatory biomarkers, and how they may influence both the success of anesthesia and the intensity of postoperative pain. By analyzing blood samples and clinical outcomes, the study will provide new insights into the role of systemic inflammation in anesthesia effectiveness and postoperative pain control. The findings may help clinicians predict anesthetic success and improve pain management strategies in dental practice.

Pulpitis is among the most common causes of orofacial pain. Irreversible pulpitis is characterized by a painful pulpal response to thermal stimuli that does not subside immediately after the removal of the stimulus. Pain is an unpleasant experience associated with actual or potential tissue damage. It is a subjective concept, and the pain threshold varies among individuals. Cold and heat tests are widely used in clinical practice for the diagnosis of symptomatic irreversible pulpitis. Irreversible pulpitis mainly arises due to infection caused by dental caries or the loss of restoration seal and microleakage. Dental trauma, pulpal exposure, and cracks can also lead to severe pulpitis. Pain associated with irreversible pulpitis accounts for more than 45% of emergency dental visits.

A detailed history of pain is essential, and it is often described as severe, dull, and throbbing; this pain may intensify with thermal or postural changes and can result in sleep disturbance. It tends to persist for prolonged periods (minutes to hours) and is generally unresponsive to analgesics. Patients also frequently report spontaneous and unprovoked sharp pains.

Achieving successful pulpal anesthesia during endodontic treatment of teeth with symptomatic irreversible pulpitis is critical for patient pain and stress management; however, this remains particularly challenging in mandibular teeth due to the inability of the inferior alveolar nerve block (IANB) to consistently provide profound anesthesia. Increased acidity in the inflamed pulp reduces the amount of basic anesthetic penetrating the nerve membrane, thereby delaying or preventing pulpal anesthesia.

Lip numbness, which typically occurs after anesthesia (i.e., loss of tactile sensation due to A-beta fiber blockade), is commonly regarded as an indicator that pulpal pain fibers (C and A-delta fibers) are also anesthetized and that the patient is ready for treatment. However, while tactile sensation is mediated by A-beta fibers, pain is transmitted via C and A-delta fibers. Local anesthetics block thick myelinated A-beta fibers and thin myelinated A-delta fibers at much lower concentrations than unmyelinated C fibers. Local anesthetics thus preferentially block myelinated fibers. Therefore, in healthy patients, the presence of lip numbness may be misleading for assessing pulpal anesthesia success. In patients with irreversible pulpitis, this method of assessment is even more unreliable.

**Several theories have been proposed to explain anesthetic failure. However, no studies have investigated the relationship between systemic inflammation and anesthetic success. The systemic immune-inflammation index (SII) is a novel biomarker for inflammation and is calculated as (neutrophil count × platelet count) / lymphocyte count. In our study, SII and other inflammatory markers will be evaluated. These additional inflammatory indices are as follows:

Aggregate index of systemic inflammation (AISI) = neutrophil count × monocyte count × platelet count / lymphocyte count

Platelet-to-lymphocyte ratio (PLR) = platelet count / lymphocyte count

Systemic inflammatory index (SII) = neutrophil count / PLR

Neutrophil-to-lymphocyte ratio (NLR) = neutrophil count / lymphocyte count.**

Moreover, although NLR has been used as an indicator of the inflammatory response in numerous diseases, there are insufficient data regarding its effects on postoperative pain, which is closely associated with acute inflammation. The aim of this study is to investigate the effects of systemic inflammatory markers, particularly SII and NLR, on the success of inferior alveolar nerve block anesthesia and postoperative pain.

Inclusion Criteria:

• Patients aged between 18 and 65 years.

Patients with a pain score greater than 54 on the Heft-Parker Visual Analog Scale (VAS).

Patients classified as ASA I according to the American Society of Anesthesiologists (ASA).

Teeth with probing depths less than 3 mm, suitable for rubber dam placement and restoration.

Vital mandibular molar teeth with a clinical diagnosis of irreversible pulpitis, confirmed by pulp vitality tests (electric pulp testing and cold testing).

Presence of bleeding upon access to the pulp chamber.

No use of non-steroidal anti-inflammatory drugs (NSAIDs) within the last 12 hours.

Absence of allergy to articaine.

Patient's consent to provide a blood sample.

Exclusion Criteria:

• Patients classified as ASA II or higher.

Pregnant women or those with suspected pregnancy.

Patients with periodontal pockets greater than 3 mm in the involved tooth.

Patients who received treatment with NSAIDs within the last 12 hours.

Patients allergic to articaine.

Teeth that had undergone previous endodontic treatment.

Teeth with extensive structural loss preventing rubber dam isolation.

Presence of internal or external root resorption.

Adult patients (18-65 years) requiring mandibular dental treatment under inferior alveolar nerve block anesthesia at Atatürk University Faculty of Dentistry, Department of Endodontics.