Evaluation of Pulpal and Salivary Neuropeptides in Dental Pain

NCT07330024 | Completed

• 1 other identifier: HRÜ/24.15.46
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This observational cross-sectional study is designed to evaluate pulpal and salivary levels of Substance P (SP) and Calcitonin Gene-Related Peptide (CGRP) in individuals with and without dental pain. The study aims to assess the associations between neuropeptide levels, pain severity, histopathological pulpal inflammation, and psychological status including depression, anxiety, and stress. By integrating biological and psychosocial parameters, this study seeks to contribute to a comprehensive understanding of the multifactorial nature of dental pain.

Conditions

Anxiety; Dental Pain; Pulpitis; Pulpal Inflammation; Psychological Stress

Keywords

Dental Pain; Substance P; Calcitonin Gene-Related Peptide; Saliva Biomarkers; Pulpal Inflammation; Psychological Stress; Anxiety; Depression

Outcome Measures

Primary Outcomes (3)

• Pulpal Calcitonin Gene-Related Peptide (CGRP) Concentration

  Calcitonin Gene-Related Peptide (CGRP) concentration measured in pulpal tissue samples collected during routine endodontic access. CGRP levels are quantified using enzyme-linked immunosorbent assay (ELISA) and expressed as picograms per milligram of pulp tissue (pg/mg). Higher values indicate increased neurogenic activity and pulpal stress.

  Periprocedural (single assessment at the time of endodontic access)

• Salivary Substance P (SP) Concentration - Baseline

  Substance P (SP) concentration measured in unstimulated whole saliva samples collected before the clinical procedure. SP levels are analyzed using enzyme-linked immunosorbent assay (ELISA) and expressed as picograms per milliliter (pg/mL). Higher values indicate increased neurogenic and stress-related activity.

  Baseline (prior to clinical procedure)

• Salivary Substance P (SP) Concentration - Periprocedural

  Substance P (SP) concentration measured in unstimulated whole saliva samples collected immediately after the clinical procedure. SP levels are analyzed using enzyme-linked immunosorbent assay (ELISA) and expressed as picograms per milliliter (pg/mL). Higher values indicate increased neurogenic and stress-related activity.

  Periprocedural (immediately after the clinical procedure; single assessment)

Secondary Outcomes (4)

• Dental Pain Severity (Verbal Rating Scale - VRS)

  Baseline (at clinical examination prior to treatment)

• Psychological Status - Depression Anxiety Stress Scale-21 (DASS-21)

  Baseline (at clinical examination prior to treatment)

• Histopathological Pulpal Inflammation Score

  Periprocedural (after pulp tissue collection during endodontic access)

• Correlation Between Neuropeptide Levels and Psychological Parameters

  Baseline (single assessment during study participation)

Study Arms (2)

Painful Group

Participants presenting with dental pain who require endodontic treatment and report pain based on clinical examination and Verbal Rating Scale assessment.

Painless Group

Participants without dental pain who require endodontic treatment and report no pain based on clinical examination and Verbal Rating Scale assessment.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of adult individuals aged 18 to 65 years who present to a university dental hospital and require endodontic treatment for permanent teeth. Participants include individuals with dental pain and individuals without dental pain, classified based on clinical examination and pain assessment. All participants are systemically healthy or have ASA physical status I or II and provide written informed consent prior to participation.

You may qualify if:

• Adults aged 18-65 years
• ASA physical status I or II
• Presence of permanent teeth requiring endodontic treatment
• Ability to understand the study procedures and provide written informed consent
• No use of analgesic medications within 24 hours prior to clinical assessment
• No food or drink intake within 2 hours prior to saliva sampling

You may not qualify if:

• Periodontal disease (probing depth \>4 mm or bleeding on probing \>20%)
• Systemic inflammatory, autoimmune, neuropathic, or chronic pain disorders
• Acute infection, fever, or antibiotic use within the last 7 days
• Pregnancy or lactation
• Regular use of psychiatric medications (e.g., antidepressants, anxiolytics, antipsychotics, antiepileptics)
• Tobacco use or alcohol consumption within the last 24 hours
• Previous endodontic treatment or history of dental trauma in the study tooth
• Systemic diseases that may affect neuropeptide levels (e.g., diabetes mellitus, thyroid disorders, renal or hepatic disease)
• Use of medications affecting salivary flow

Sponsors & Collaborators

• Kahramanmaras Sutcu Imam University: lead

Study Sites (1)

Kahramanmaraş Sutcu İmam University, Faculty of Dentistry

Kahramanmaraş, onikişubat, 46010, Turkey (Türkiye)

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Pulp tissue and unstimulated saliva samples collected during routine endodontic procedures and retained for biochemical analysis of Substance P and Calcitonin Gene-Related Peptide. No DNA extraction is performed.

MeSH Terms

Conditions

Toothache; Pulpitis; Stress, Psychological; Anxiety Disorders; Depression

Condition Hierarchy (Ancestors)

Tooth Diseases; Stomatognathic Diseases; Facial Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Dental Pulp Diseases; Behavioral Symptoms; Behavior; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof.

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: January 9, 2026
• Study Start: November 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: November 15, 2025
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)