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

NCT07644065 | Completed

• 2 other identifiers: DPDT-12/2019Protocol No. P-604/28.02.2020
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Impacted Third Molar; Postoperative Pain; Neuroinflammation; Anxiety

Keywords

kynurenic acid; serotonin; kynurenine pathway; IDO; third molar surgery; perioperative biomarker; Pederson index; postoperative pain

Outcome Measures

Primary Outcomes (2)

• 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

  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

  Preoperative baseline and 24 hours postoperative at each operation

Secondary Outcomes (3)

• Postoperative pain intensity

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

• State anxiety

  Preoperative baseline at each operation

• KYNA variation across Pederson surgical difficulty grades

  24 hours postoperative at Operation 1

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Identical-appearing capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=10.

Drug: Placebo

Ibuprofen

ACTIVE COMPARATOR

Ibuprofen 400 mg oral capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=15

Drug: Ibuprofen

Ibuprofen + Gabapentin

EXPERIMENTAL

Ibuprofen 400 mg plus Gabapentin 300 mg oral capsules administered 1 hour before incision, repeated every 8 hours for 24 hours. N=15

Drug: Ibuprofen + Gabapentin

Interventions

Placebo DRUG

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

Placebo

Ibuprofen DRUG

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

Ibuprofen

Ibuprofen + Gabapentin DRUG

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

Ibuprofen + Gabapentin

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

Sponsors & Collaborators

• Plovdiv Medical University: lead
• Radka Ivanova Masaldzhieva, Dept. of Health Care Management, Faculty of Public Health, MU-Plovdiv: collaborator
• Mariya Vlado Ivanovska, Dept. of Microbiology and Immunology, Faculty of Medicine, MU-Plovdiv: collaborator
• Ralitsa Dimitrova Raycheva, Dept. of Social Medicine and Public Health, Faculty of Public Health, MU-Plovdiv: collaborator

Study Sites (1)

Faculty of Dental Medicine

Plovdiv, 4002, Bulgaria

Location

MeSH Terms

Conditions

Pain, Postoperative; Neuroinflammatory Diseases; Anxiety Disorders

Interventions

Ibuprofen; Gabapentin

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Nervous System Diseases; Inflammation; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Amines; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Cyclohexanecarboxylic Acids; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Deyan Neychev, MD, PhD

  Medical University of Plovdiv

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind achieved using identical-appearing capsules. Biochemical analyses performed blinded to surgical timepoint and pharmacological group allocation.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Each participant underwent two sequential surgical procedures (bilateral impacted mandibular third molar extractions) separated by a two-week interval, serving as their own control across both operative exposures.

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 12, 2026
• Study Start: September 30, 2019
• Primary Completion: May 17, 2020
• Study Completion: September 30, 2020
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)