Anxiety, Impacted Third Molar, Neuroinflammation, Postoperative Pain
Conditions
Keywords
kynurenic acid, serotonin, kynurenine pathway, IDO, third molar surgery, perioperative biomarker, Pederson index, postoperative pain
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.
Detailed description
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.
Interventions
DRUGPlacebo
Identical-appearing oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.
DRUGIbuprofen
Ibuprofen 400 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.
DRUGIbuprofen + Gabapentin
Ibuprofen 400 mg plus Gabapentin 300 mg oral capsules administered preemptively 1 hour before incision and every 8 hours for 24 hours.
Sponsors
Plovdiv Medical University
Radka Ivanova Masaldzhieva, Dept. of Health Care Management, Faculty of Public Health, MU-Plovdiv
Mariya Vlado Ivanovska, Dept. of Microbiology and Immunology, Faculty of Medicine, MU-Plovdiv
Ralitsa Dimitrova Raycheva, Dept. of Social Medicine and Public Health, Faculty of Public Health, MU-Plovdiv
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind achieved using identical-appearing capsules. Biochemical analyses performed blinded to surgical timepoint and pharmacological group allocation.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 38 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum kynurenic acid (KYNA) concentration | 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 |
| Serum serotonin concentration | 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
| Measure | Time frame | Description |
|---|---|---|
| Postoperative pain intensity | 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) |
| State anxiety | Preoperative baseline at each operation | Preoperative state anxiety assessed using the State-Trait Anxiety Inventory (STAI Form Y), State subscale |
| KYNA variation across Pederson surgical difficulty grades | 24 hours postoperative at Operation 1 | Serum KYNA at 24 hours postoperative compared across Pederson difficulty grades (5-9), assessed by Kruskal-Wallis test |
Countries
Bulgaria
Contacts
PRINCIPAL_INVESTIGATORDeyan Neychev, MD, PhD
Medical University of Plovdiv
Outcome results
None listed