Neuropeptides substance P and neurokinin A were significantly elevated in inflamed dental pulp and gum fluid, correlated with pain severity, and dropped significantly within one week after root canal treatment.
Significant elevation in all 4 markers (P<0.001)Neuropeptides NKA and SP plus inflammatory markers IL-8 and MMP-8 were all significantly higher in inflamed pulp and surrounding gum fluid, with levels correlating to pain severity
What the researchers found
All four mediators (NKA, SP, IL-8, MMP-8) were significantly higher in pulpitis pulp tissue compared to healthy pulp (NKA: P<0.001, SP: P=0.005, IL-8: P<0.001, MMP-8: P<0.001). The same pattern was seen in gingival crevicular fluid (NKA: P=0.01, SP: P<0.001, IL-8: P=0.001, MMP-8: P<0.001). One week after root canal treatment, all mediator levels decreased significantly in GCF. SP, IL-8, and MMP-8 levels were higher in patients with higher pain scores than those with lower pain scores.
Why it matters
Understanding which molecular signals drive tooth pain has implications for developing targeted pain treatments. Substance P and neurokinin A are well-known pain and inflammation neuropeptides, and their elevation in pulpitis confirms their role in dental pain. The finding that gum fluid levels reflect pulp inflammation opens the possibility of non-invasive diagnostic testing — potentially detecting pulp disease through a simple gum fluid sample rather than requiring invasive pulp access.
How the study worked
Clinical study of 40 patients — 20 with healthy teeth and 20 with symptomatic irreversible pulpitis. Pulp tissue and gingival crevicular fluid (GCF) samples were collected from both groups. GCF sampling was repeated one week after root canal treatment. NKA, SP, IL-8, and MMP-8 levels were measured by ELISA. GCF from contralateral healthy teeth served as controls. Statistical analysis included t-tests, ANOVA, Kruskal-Wallis, Mann-Whitney U, and Pearson correlation.
What this study cannot tell us
Relatively small sample size (40 patients). The study measured associations between peptide levels and inflammation/pain but cannot establish causation. Pain scoring is subjective and variable between patients. GCF collection technique can affect sample quality. Only a one-week follow-up after treatment was included. The study did not test whether blocking these neuropeptides would reduce dental pain.
How to read the evidence
This is a small clinical study with appropriate controls and statistical analysis. The consistent elevation of all four markers across two tissue types strengthens the findings, though the sample size limits generalizability and the study is observational rather than interventional.
When this study was published
Published in 2020 in the Journal of Endodontics, this study contributes to the growing understanding of neuropeptide involvement in dental pain and inflammation.
The bigger picture
Substance P and neurokinin A are tachykinin neuropeptides that play central roles in pain transmission and neurogenic inflammation throughout the body. NK1 receptor antagonists (blocking substance P) have been developed for various pain conditions. Understanding how these peptides contribute to dental pain could lead to targeted therapies — NK1 or NK2 receptor antagonists applied locally in the tooth — that address the molecular cause of pain rather than relying on broad-acting analgesics or antibiotics.
Questions still open
- Could NK1 receptor antagonists (substance P blockers) be applied locally to treat dental pain before or during root canal procedures?
- Can GCF neuropeptide levels be developed into a clinical diagnostic test for early detection of pulp inflammation?
- Do neurokinin A and substance P levels predict which teeth will progress from reversible to irreversible pulpitis?
Common questions
What are substance P and neurokinin A?
Could this lead to better treatments for toothache?
Read the original research
Comparison of Neurokinin A, Substance P, Interleukin 8, and Matrix Metalloproteinase-8 Changes in Pulp tissue and Gingival Crevicular Fluid Samples of Healthy and Symptomatic Irreversible Pulpitis Teeth.
Journal of endodontics, 46(10), 1428-1437
Citation
Akbal Dincer, Gozde; Erdemir, Ali; Kisa, Ucler. (2020). Comparison of Neurokinin A, Substance P, Interleukin 8, and Matrix Metalloproteinase-8 Changes in Pulp tissue and Gingival Crevicular Fluid Samples of Healthy and Symptomatic Irreversible Pulpitis Teeth.. Journal of endodontics, 46(10), 1428-1437. https://doi.org/10.1016/j.joen.2020.07.013