Systematic review and meta analysis of substance P in gingival crevicular fluid as a diagnostic biomarker for tooth pain

Abstract Background The trigeminal sensory system releases numerous neuropeptides like neurokinin A (NKA), substance P (SP), and calcitonin gene-regulated protein (CGRP), which play crucial functions in orofacial pain. Pulpitis increases the production of these neuropeptides in pulp and peripheral body fluids like saliva and the GCF. Pain perception is the most investigated and well-researched role of SP. Moreover, SP was the first neuropeptide to be recognized in dental pulp. Methods Searches were performed in PubMed, Scopus, EBSCOhost, Epistemonikos, grey literature databases, and other available databases until July 2024. Three independent reviewers performed a grey literature search on Google to attain maximum coverage beyond peer review, and articles were resolved with agreement among the reviewers. The selection criteria were in vivo studies that evaluated SP levels in GCF at the site of tooth pain and a healthy tooth. Meta-analysis was performed using standardized mean differences by the method of Cohen using the random-effects inverse variance model with the DerSimonian-Laird estimator for tau². Results Six articles were included in the review according to the selection criteria. Five studies concluded that there is a significant elevation of levels of SP in GCF in a painful tooth when compared to a healthy tooth. These five studies were incorporated in the meta-analysis. However, one study concluded similar levels of SP in GCF in painful and healthy teeth. Conclusions The results indicate that SP concentrations in GCF could rise due to dental pain and inflammation. These findings must be interpreted conservatively since several possible confounding factors, such as differences in sampling methods, pain determination criteria, patient age, systemic health status, drug use, and periodontal status, could affect SP levels. Due to the paucity of studies and heterogeneity of methods, more high-quality research must be conducted to replicate these associations and define the clinical usefulness of SP as a pain biomarker for dentistry.