Kynurenic Acid and Serotonin as Perioperative Neuroinflammatory Biomarkers in Sequential Third Molar Surgery

Plovdiv Medical University40 enrolled

Overview

A prospective cohort of 40 consecutive patients with bilateral impacted mandibular third molars underwent two sequential surgical extractions separated by a two-week interval. Serum kynurenic acid (KYNA) and serotonin were measured preoperatively and 24 hours after each procedure. The study examined longitudinal dynamics of kynurenine pathway biomarkers, their variation across Pederson surgical difficulty grades, and their relationship with postoperative pain and state anxiety.

Participants were randomised to placebo, ibuprofen 400 mg, or ibuprofen 400 mg plus gabapentin 300 mg administered preemptively 1 hour before incision and continued at 8-hourly intervals for 24 hours. Blood samples were collected at four timepoints (T0 Op1, T24 Op1, T0 Op2, T24 Op2) and analysed by ELISA for serum KYNA and serotonin. Postoperative pain was assessed by VAS at 2, 6, 12, 24, 48, and 72 hours. State-trait anxiety was assessed using the STAI Form Y before each operation. Pederson difficulty index was applied independently by two calibrated examiners. The biomarker analysis is reported observationally with pharmacological allocation treated as a covariate. Clinical data and samples were collected at the Department of Oral Surgery, Faculty of Dental Medicine, Medical University of Plovdiv, Bulgaria, during 2017-2018; laboratory biomarker analyses were conducted under Project No. DPDT-12/2019, Medical University of Plovdiv, and completed in 2020.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Impacted Third Molar

Interventions

PlaceboDRUG

Identical-appearing oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.

IbuprofenDRUG

Ibuprofen 400 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.

Ibuprofen + GabapentinDRUG

Ibuprofen 400 mg plus Gabapentin 300 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 38 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Bilateral impacted mandibular third molars requiring surgical extraction * Age 18-38 years * Written informed consent * Ability to comply with study procedures Exclusion Criteria: * Systemic inflammatory disease * Autoimmune disease * Neurological disease * Psychiatric disorders * Chronic pain conditions * Use of immunomodulatory medications * Use of psychotropic medications * Use of analgesic medications * Pregnancy * Drug hypersensitivity * Active pericoronitis at enrollment

Outcomes

Primary Outcomes

Serum kynurenic acid (KYNA) concentration

Change in serum KYNA from preoperative baseline (T0) to 24 hours postoperative (T24) at each of two sequential operations, assessed by ELISA

Time frame: Preoperative baseline and 24 hours postoperative at each operation

Serum serotonin concentration

Change in serum serotonin from preoperative baseline (T0) to 24 hours postoperative (T24) at each of two sequential operations, assessed by ELISA

Time frame: Preoperative baseline and 24 hours postoperative at each operation

Secondary Outcomes

Postoperative pain intensity

Pain assessed using a 100 mm Visual Analogue Scale (VAS; 0 = no pain, 100 = worst imaginable pain)

Time frame: 2, 6, 12, 24, 48, and 72 hours postoperative at each operation

State anxiety

Preoperative state anxiety assessed using the State-Trait Anxiety Inventory (STAI Form Y), State subscale

Time frame: Preoperative baseline at each operation

KYNA variation across Pederson surgical difficulty grades

Serum KYNA at 24 hours postoperative compared across Pederson difficulty grades (5-9), assessed by Kruskal-Wallis test

Time frame: 24 hours postoperative at Operation 1