Many studies have been conducted recently to identify biomarkers that could potentially be used to objectively evaluate pain.


To synthesize and critically analyze primary studies of endogenous biomarkers and their associations with pain to identify suitable biomarkers for the objective evaluation of pain in critically ill children.


PubMed, Scopus, and Ovid databases were searched; searches were restricted by publication date, language, species, and participant age. Critical appraisal tools and the Strengthening the Reporting of Observational Studies in Epidemiology checklist were used to evaluate quality of evidence.


All included articles were coded according to methods and findings. Saliva, blood, cerebrospinal fluid, and gingival crevicular fluid were used to detect biomarkers. Enzyme-linked immunosorbent assays were used in most studies (64%). Appropriate statistical analyses were performed at a significance level of P < .05 in included studies. Cytokines, peptides, and hormones were associated with pain, stress, and inflammatory response, suggesting that they can be used to screen for pain in children during painful conditions. Only 1 study in neonates did not show any correlation between saliva biomarkers and pain.


According to this literature review, various biomarkers that are easily obtained and measured in a clinical setting are associated with pain in children. Further investigation of these biomarkers through observational studies is suggested to evaluate their suitability for pain assessment in critically ill children.

You do not currently have access to this content.