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.

Authors

Aliye Kamalak, Esra Balkanlıoğlu, Hilmi Taş, Rabia Hurşitoğlu, Hasan Dağlı

Published in

BMC oral health. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Dental pain is influenced by both local inflammatory processes and neurobiological and psychological factors. This study compared substance P (SP) and calcitonin gene-related peptide (CGRP) levels in pulp tissue and unstimulated saliva between patients with dental pain and painless controls, and investigated their relationships with pain severity, pulpal inflammation, and psychological distress.
Fifty-two adult patients indicated for primary endodontic treatment were enrolled and allocated into two groups: 26 patients with dental pain and 26 painless controls with no pain complaint and a VRS score of 0. Pain intensity was assessed using the Verbal Rating Scale (VRS). Depression, anxiety, and stress were evaluated using the Depression Anxiety Stress Scale-21 (DASS-21). Pulp tissue and unstimulated saliva samples were collected and analyzed using enzyme-linked immunosorbent assay. Pulpal inflammation was graded histopathologically. Between-group comparisons were performed using independent samples t-tests or Mann-Whitney U tests, as appropriate. Effect sizes were calculated using eta squared (η²). Correlations were assessed using Pearson or Spearman coefficients to examine associations between neuropeptide levels, pain severity, and inflammation grade.
Pulp calcitonin gene-related peptide levels were significantly higher in patients with dental pain than in painless controls (p = 0.007; η² = 0.146). Salivary substance P levels were also significantly increased in the painful group (p = 0.044; η² = 0.080). No significant between-group differences were observed for pulp substance P or salivary calcitonin gene-related peptide (p > 0.05). Depression, anxiety, and stress scores were all significantly higher in patients with dental pain (all p < 0.001). Pain severity showed positive correlations with pulp calcitonin gene-related peptide (r = 0.332) and salivary substance P (r = 0.324), whereas no significant association was found between pain severity and histopathological inflammation grade.
Pulp calcitonin gene-related peptide may be associated with local neurogenic activation in symptomatic pulpal pain, while salivary substance P may represent a potential noninvasive candidate marker for pain-associated responses. However, the lack of consistent pulp-saliva correspondence indicates that salivary biomarkers should not be considered direct surrogates of pulpal neuropeptide activity.
ClinicalTrials.gov Identifier: NCT07330024.

PMID:
42458416
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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