Status
Completed
Phase
Not applicable
Enrollment
72
Locations
1
Results
Not posted
Publications
1
Study 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.
Dental pain is a multifactorial condition influenced by peripheral inflammatory processes, neurogenic mechanisms, and psychological factors. Neuropeptides such as Substance P (SP) and Calcitonin Gene-Related Peptide (CGRP) are known to play an important role in pain transmission and pulpal inflammatory responses. However, the invasive nature of pulpal sampling limits the routine clinical application of pulpal biomarkers, emphasizing the need to investigate non-invasive biological media such as saliva. This observational cross-sectional study includes adult participants who require endodontic treatment and are categorized into painful and painless groups based on clinical examination and pain assessment using the Verbal Rating Scale (VRS). Pulp tissue samples are obtained during routine endodontic access procedures, and unstimulated saliva samples are collected before and after the clinical procedure. Levels of SP and CGRP in pulp and saliva samples are measured using enzyme-linked immunosorbent assay (ELISA). Psychological status is evaluated using the Depression Anxiety Stress Scale-21 (DASS-21) to assess levels of depression, anxiety, and stress. Pulpal inflammation is evaluated through histopathological examination of pulp tissue samples using a semi-quantitative scoring system. The primary objective of this study is to evaluate the relationship between dental pain and pulpal and salivary neuropeptide levels. Secondary objectives include assessing the associations between neuropeptides, psychological status, pain severity, and histopathological pulpal inflammation. The study is designed to provide descriptive and associative data without intervention, supporting a biopsychosocial framework for understanding dental pain and exploring the potential clinical relevance of salivary biomarkers.
Interventions
No intervention details reported.
Timeline
First posted
Jan 9, 2026
Study start
Nov 1, 2024
Primary completion
Sep 1, 2025
Study completion
Nov 15, 2025
Results posted
Not reported
Registry updated
Jan 9, 2026
Outcomes
Pulpal Calcitonin Gene-Related Peptide (CGRP) Concentration
Time frame · Periprocedural (single assessment at the time of endodontic access)
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.
Salivary Substance P (SP) Concentration - Baseline
Time frame · Baseline (prior to clinical procedure)
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.
Salivary Substance P (SP) Concentration - Periprocedural
Time frame · Periprocedural (immediately after the clinical procedure; single assessment)
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.
Dental Pain Severity (Verbal Rating Scale - VRS)
Time frame · Baseline (at clinical examination prior to treatment)
Dental pain severity assessed using the Verbal Rating Scale (VRS) with the following categories: 0 = No pain 1. = Mild pain 2. = Moderate pain 3. = Severe pain The scale ranges from 0 to 3, with higher scores indicating greater pain severity.
Psychological Status - Depression Anxiety Stress Scale-21 (DASS-21)
Time frame · Baseline (at clinical examination prior to treatment)
Psychological status assessed using the Depression Anxiety Stress Scale-21 (DASS-21), consisting of three subscales: depression, anxiety, and stress. Each subscale score ranges from 0 to 42, with higher scores indicating worse psychological status.
Histopathological Pulpal Inflammation Score
Time frame · Periprocedural (after pulp tissue collection during endodontic access)
Degree of pulpal inflammation assessed by histopathological examination of pulp tissue samples using a semi-quantitative scoring system: 0 = No inflammation 1. = Mild inflammation 2. = Moderate inflammation 3. = Severe inflammation Higher scores indicate greater inflammatory severity.
Correlation Between Neuropeptide Levels and Psychological Parameters
Time frame · Baseline (single assessment during study participation)
Correlation analysis between: Pulpal CGRP concentration (pg/mg), Salivary Substance P concentration (pg/mL), and Psychological parameters (depression, anxiety, stress scores measured by DASS-21). Associations are evaluated using appropriate statistical correlation analyses. This outcome does not represent a new biological measurement but an analytical relationship between predefined outcomes.
Eligibility
Inclusion Criteria: * 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 Exclusion Criteria: * 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
Study locations
Turkey (Türkiye). Showing up to 24 locations stored in the fast local snapshot.
Kahramanmaraş Sutcu İmam University, Faculty of Dentistry
Kahramanmaraş, onikişubat, Turkey (Türkiye)
Related trials
Fundación de Investigación Biomédica - Hospital Universitario de La Princesa · Migraine · Headache
Not applicable
Completed
513
2026-07
Jordan University of Science and Technology · Root Canal Treatment · Postoperative Pain
Not applicable
Active, not recruiting
75
2026-07
Tanta University · Calcitonin · Subcutaneous
Phase 3
Recruiting
168
2026-07
Insel Gruppe AG, University Hospital Bern · Acute Mountain Sickness
Phase 4
Not yet recruiting
30
2026-07
Institut Claudius Regaud · Medullary Thyroid Cancer
Not applicable
Completed
24
2026-06
Rigmor Højland Jensen · Idiopathic Intracranial Hypertension (IIH)
Phase 3
Not yet recruiting
96
2026-06
IRCCS San Raffaele Roma · Episodic Migraine · Chronic Migraine
Not applicable
Recruiting
2,641
2026-06
Pamukkale University · Neck Pain · Text Neck Syndrome
Not applicable
Completed
38
2026-05
Related PeptideStat pages
Research pages describe evidence. Vendor pages, where available, describe independently tracked research-product listings and are not clinical recommendations.