Dental PainPAIN-SPCGRPNCT07330024
Evaluation of Pulpal and Salivary Neuropeptides in Dental Pain
An observational study of Dental Pain and Pulpitis, run by Kahramanmaras Sutcu Imam University at 1 site in Turkey (Türkiye).
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Dental Pain, Pulpitis, Pulpal Inflammation
- How many people
- 72 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 Nov 2024to 15 Nov 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Kahramanmaraş Sutcu İmam University, Faculty of Dentistry
Kahramanmaraş, onikişubat, 46010
About this study
Official title: Evaluation of Salivary and Pulpal Levels of Substance P and Calcitonin Gene-Related Peptide in Relation to Dental Pain, Pulpal Inflammation, and Psychological Status
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.
Read the detailed description
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.
- Conditions
- Dental Pain, Pulpitis, Pulpal Inflammation, Psychological Stress, Anxiety
- Keywords
- Dental Pain, Substance P, Calcitonin Gene-Related Peptide, Saliva Biomarkers, Pulpal Inflammation, Psychological Stress, Anxiety, Depression
- Medical subject headings
- Toothache, Pulpitis, Stress, Psychological, Anxiety Disorders, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Periprocedural (immediately after the clinical procedure; single assessment)
Secondary outcomes (4)
Dental Pain Severity (Verbal Rating Scale - VRS)
Dental pain severity assessed using the Verbal Rating Scale (VRS) with the following categories:
0 = No pain
- = Mild pain
- = Moderate pain
- = Severe pain
The scale ranges from 0 to 3, with higher scores indicating greater pain severity.
Measured: 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.
Measured: 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
- = Mild inflammation
- = Moderate inflammation
- = Severe inflammation
Higher scores indicate greater inflammatory severity.
Measured: 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.
Measured: Baseline (single assessment during study participation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2026
- Study start1 Nov 2024
- Primary completion1 Sep 2025
- Study completion15 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Dental PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kahramanmaras Sutcu Imam University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aliye Kamalak, Kahramanmaras Sutcu Imam University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07330024
- Sponsor's protocol ID
- HRÜ/24.15.46
- Other IDs
- HRÜ/24.15.46
- Acronym
- PAIN-SPCGRP
- Status last verified
- Jan 2026
- First submitted
- 12 Dec 2025
- Last updated
- 9 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: De-identified individual participant data (IPD) will not be shared due to ethical restrictions, institutional policies, and the sensitive nature of biological and psychological data collected in this study.
Publications
Kamalak A, Balkanlioglu E, Tas H, Hursitoglu R, Dagli H. Association between calcitonin gene-related peptide and substance P in saliva and pulp according to anxiety levels in patients with dental pain: a cross-sectional study. BMC Oral Health. 2026 Jul 15. doi: 10.1186/s12903-026-09288-1. Online ahead of print.
PubMed 42458416
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Salivary and Pulpal Levels of Substance P and Calcitonin Gene-Related Peptide in Relation to Dental Pain, Pulpal Inflammation, and Psychological Status
- ClinicalTrials.gov ID
- NCT07330024
- Acronym / sponsor ID
- PAIN-SPCGRP / HRÜ/24.15.46
- Conditions
- Dental Pain, Pulpitis, Pulpal Inflammation, Psychological Stress, Anxiety
- Keywords
- Dental Pain, Substance P, Calcitonin Gene-Related Peptide, Saliva Biomarkers, Pulpal Inflammation, Psychological Stress, Anxiety, Depression
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Kahramanmaras Sutcu Imam UniversityUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- 1 Sep 2025 (actual)
- Study completion
- 15 Nov 2025 (actual)
- First posted
- 9 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Observational model
- Other
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
4 secondary outcomes
Dental Pain Severity (Verbal Rating Scale - VRS)
Time frame: Baseline (at clinical examination prior to treatment)
Psychological Status - Depression Anxiety Stress Scale-21 (DASS-21)
Time frame: Baseline (at clinical examination prior to treatment)
Histopathological Pulpal Inflammation Score
Time frame: Periprocedural (after pulp tissue collection during endodontic access)
Correlation Between Neuropeptide Levels and Psychological Parameters
Time frame: Baseline (single assessment during study participation)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2026.
- Derived from this study: PubMed 42458416Kamalak A, Balkanlioglu E, Tas H, Hursitoglu R, Dagli H. Association between calcitonin gene-related peptide and substance P in saliva and pulp according to anxiety levels in patients with dental pain: a cross-sectional study. BMC Oral Health. 2026 Jul 15. doi: 10.1186/s12903-026-09288-1. Online ahead of print.
- Individual participant dataSharing planned: No. De-identified individual participant data (IPD) will not be shared due to ethical restrictions, institutional policies, and the sensitive nature of biological and psychological data collected in this study.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Dental Pain and Pulpitis, run by Kahramanmaras Sutcu Imam University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pulpal Calcitonin Gene-Related Peptide (CGRP) Concentration (time frame: Periprocedural (single assessment at the time of endodontic access)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07330024, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2026.