Journal Article

Reliability of Potential Pain Biomarkers in the Saliva of Healthy Subjects: Inter-Individual Differences and Intersession Variability

Cuadrado-Asensio, Rubén, Maldonado, Miguel J., Sobas, Eva M., Reinoso, Roberto, Fernández, Itziar, Pastor, José C.

2016

Overview

Salivary cortisol, α-amylase (sAA), secretory IgA (sIgA), testosterone, and soluble fraction of receptor II of TNFα (sTNFαRII) could serve as objective pain measures, but the normal variability of these potential biomarkers is unknown. Saliva was collected with the passive secretion method from 34, pain-free subjects in two single samples at least 24 hours apart. Biomarker variation and intersession reliability were assessed with the intraclass correlation coefficient (ICC). Also, we calculated the within-subject standard deviation (Sw) and the reproducibility (2.77 × Sw) of intersession measures. Salivary cortisol, sAA, sIgA, testosterone, and sTNFαRII yielded the following ICCs: 0.53, 0.003, 0.88, 0.42 and 0.83, respectively. We found no statistically significant systematic differences between sessions in any biomarker except for testosterone, which showed a decrease on the second day (p<0.001). The reproducibility for salivary cortisol, sAA, sIgA, testosterone, and sTNFαRII were 0.46 ng/ml, 12.88 U/ml, 11.7 μg/ml, 14.54 pg/ml and 18.29 pg/ml, respectively. Cortisol, testosterone and TNFαRII measurement variability showed a positive correlation with the magnitude (p<0.002), but no relationship was found for sAA and sIgA. Salivary sIgA and sTNFαRII show a remarkable good reproducibility and, therefore, could be useful as pain biomarkers. When using the passive secretion method, intersession variations in salivary sIgA of more than 11.7 μg/ml may reflect true biomarker change. In the case of sTNFαRII this will depend of the magnitude. The estimates herein provided should help investigators and clinicians differentiate actual biomarker modification from measurement variability.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / alpha-Amylases - metabolism / Analysis / Bioengineering / Bioindicators / Biological markers / Biology and Life Sciences / Biomarkers / Biomarkers - metabolism / Biomedical materials / Chronic pain / Coefficient of variation / Correlation / Correlation analysis / Correlation coefficient / Correlation coefficients / Cortisol / Diagnosis / Female / Health aspects / Healthy Volunteers / Hormones / Humans / Hydrocortisone / Hydrocortisone - metabolism / Immunoglobulin A / Immunoglobulin A, Secretory - metabolism / Male / Mathematical analysis / Medicine and Health Sciences / Menstruation / Observer Variation / Pain / Pain - diagnosis / Pain - metabolism / Physiological aspects / Receptors, Tumor Necrosis Factor, Type II - metabolism / Reference Values / Reliability analysis / Reproducibility / Reproducibility of Results / Research and Analysis Methods / Saliva / Saliva - chemistry / Secretion / Social Sciences / Statistical analysis / Statistical methods / Studies / Testosterone / Testosterone - metabolism / Tumor necrosis factor / Tumor necrosis factor-TNF / Tumor necrosis factor-α / Variability / α-Amylase