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Completed

NCT Number: NCT07644065

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

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.

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Key information

Conditions

Impacted Third Molar Anxiety Anxiety Disorders Inflammation Mental Disorders Nervous System Diseases Neuroinflammation Neuroinflammatory Diseases Neurologic Manifestations Pain Pain, Postoperative Pathologic Processes Pathological Conditions, Signs and Symptoms Postoperative Complications Postoperative Pain Signs and Symptoms

Age range

18 year–38 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Faculty of Dental Medicine

Plovdiv, 4002, Bulgaria

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Placebo

Drug

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

Ibuprofen

Drug

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

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.

Primary outcomes

  1. Serum kynurenic acid (KYNA) concentration

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

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

  2. Serum serotonin concentration

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

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

Secondary outcomes

  1. Postoperative pain intensity

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

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

  2. State anxiety

    Time frame: Preoperative baseline at each operation

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

  3. KYNA variation across Pederson surgical difficulty grades

    Time frame: 24 hours postoperative at Operation 1

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

Sponsors and collaborators

Lead sponsor

Plovdiv Medical University

Other

Collaborators

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

Registry information

Official study title

Influence of Serotonin and Kynurenic Acid on Postoperative Pain, Neuroinflammation and Anxiety Following Surgical Removal of Impacted Mandibular Third Molars

Acronym: KYNA-3M

Important dates

Study start
2019
Primary completion
2020
Study completion
2020
First posted
Jun 12, 2026
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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