Diurnal variation of inflammatory plasma proteins involved in pain

Introduction: Proteomics is a powerful approach for biochemical research because it directly studies the main functional components of biochemical systems. The understanding of the normal fluctuations of the proteome in health is essential to identify pain-specific biomarkers. Objective: To investigate fluctuations of the plasma proteome in healthy pain-free individuals. Methods: Blood samples were structurally collected in the early morning and evening from 10 clinically healthy individuals (26.3 +/- 3.3 years). High abundant proteins were removed from plasma, and proteins were then analysed by nanoliquid chromatography combined with mass spectrometry. In addition, an assay of 71 cytokines/chemokines/growth factors was analysed. Results: Multivariate statistical analysis displayed that there were up to 64 proteins whose expression levels were significantly altered between the plasma samples collected during the morning and evening; no changes existed for the assay. The levels of 34 proteins were increased and 30 proteins were decreased during the evening compared with the morning sample. The increased proteins were involved in the biological processes such as protein activation cascade, complement activation, and stress response. The decreased proteins were involved in regulation of endopeptidase activity, inflammatory response, and protein metabolic processes. Conclusion: The circadian variations in the plasma proteome stress the need to collect blood samples of both patients and controls at a fixed time of the day. The results in this study might be useful for better understanding of the complexity of individual variation in the human plasma proteome over time and provide a baseline for improved pain biomarker discovery.