The aim of this study was to evaluate the effects of endodontic treatment on levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in the saliva of patients with symptomatic apical periodontitis.

Twelve patients with mandibular molars with symptomatic apical periodontitis were enrolled in this study. An initial saliva sample was collected just before administration of anesthesia for root canal treatment, which was performed at the first visit. A second saliva sample was collected at a control visit 1 week after treatment. Salivary SP and CGRP levels were evaluated quantitatively using biochemical assays. The data were analyzed using Pearson correlation analysis, the paired samples t-test, and the Mann-Whitney U test (p = 0.05).

The postoperative salivary level of SP was significantly lower than the preoperative level (p = 0.005). However, the postoperative salivary level of CGRP was similar to the preoperative level (p = 0.932). Visual analog scale (VAS) scores of patients' subjective pain were found to be positively correlated with salivary levels of SP (r = 0.421; p = 0.040). No statistically significant correlations were observed between salivary levels of CGRP and VAS scores for patients' subjective percussion tenderness (p = 0.533) or VAS scores for patients' subjective pain (p = 0.459).

According to the results of the present study, salivary SP levels may be used as an objective indicator in the diagnosis and assessment of the degree of pain in endodontic diseases.

Thai Clinical Trials Registry Identifier: TCTR20161228001

In the present study, three kinds of tissues cells (pulp, gingiva, and periodontal ligament) were investigated if those cells express MMP and TIMP when they were stimulated with neuropeptides (substance P, CGRP) or proinflammatory cytokine, TNF-α.

The cells cultured from human dental pulp (PF), gingiva (GF) and periodontal ligament were (PDLF) stimulated with Mock, SP, TNF-α, and CGRP for 24 hrs and 48 hrs. for an RNase protection assay and Enzyme Linked Immunosorbent Assay.

Cells (PF, GF and PDLF) seeded in 100 mm culture dish were stimulated with SP (10^-5, 10^-8 M) or only with medium (Mock stimulation) for 4hrs and for 24 hrs for RNase Protection Assay, and they were stimulated with CGRP (10^-5 M) and TNF-α (2 ng/mL) for 24 hrs and with various concentraion of TNF-α (2, 10, and 100 ng/mL) for Rnase Protection Assay with a human MMP-1 probe set including MMP 1, 2, 8, 7, 8, 9, 12, and TIMP 2, 3.

In addition, cells (PF, GF and PDLF) were stimulated with Mock and various concentraion of TNF-α (2, 10, and 100 ng/mL) for 24 hrs and with TNF-α (10 ng/mL) for 48 hrs, and the supernatents from the cells were collected for Enzyme Linked Immunosorbent Assay (ELISA) for MMP-1 and MMP-13.

The expression of MMPs in PF, GF, PDLF after stimulation with SP and CGRP were not changed compared with Mock stimulation for 4 hrs and 24 hrs. The expression of MMP-1, -12, -13 24 hrs after stimulation with TNF-α were upregulated, however the expression of TIMP-3 in PF, GF, PDLF after stimulation with TNF-α were downregulated. TNF-α (2 ng/mL, 10 ng/mL, 100 ng/mL) increased MMP-1 and MMP-12 expression in PF dose dependently for 24 hrs.

TNF-α in the area of inflammation may play an important role in regulating the remodeling of dentin, cementum, and alveolar bone.