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.
Study Type
OBSERVATIONAL
Enrollment
72
Kahramanmaraş Sutcu İmam University, Faculty of Dentistry
Kahramanmaraş, onikişubat, Turkey (Türkiye)
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.
Time frame: 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.
Time frame: 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.
Time frame: Periprocedural (immediately after the clinical procedure; single assessment)
Dental Pain Severity (Verbal Rating Scale - VRS)
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.
Time frame: Baseline (at clinical examination prior to treatment)
Psychological Status - Depression Anxiety Stress Scale-21 (DASS-21)
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.
Time frame: Baseline (at clinical examination prior to treatment)
Histopathological Pulpal Inflammation Score
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.
Time frame: Periprocedural (after pulp tissue collection during endodontic access)
Correlation Between Neuropeptide Levels and Psychological Parameters
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.
Time frame: Baseline (single assessment during study participation)
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