Proteome-based systems biology in chronic pain

Chronic pain represents a major medical challenge in the 21^st century. Enormous efforts have been invested towards deciphering the complexity of chronic pain from different angles (molecular, physiological, psychosocial, and behavioral) in both preclinical and clinical settings. While progress has been made, our understanding of the underlying mechanisms of chronic pain remains insufficient. Consequently, chronic pain treatment is often inadequate. It lacks efficacy in most patients and is associated with detrimental side effects - a situation which calls for urgent changes in pain research and management. In this review we propose that protein-centric systems biology can significantly contribute to pain research. This approach may introduce the long-awaited paradigm shift in pain research from single targets to multidimensional cellular networks. We critically discuss how recent advances in reproducible and comprehensive proteome profiling can be exploited by pain researchers in the following ways: to gain mechanistic insights into chronic pain and its diverse forms, to facilitate clinical trials and the search for new drug targets, and to objectively assess chronic pain and its stages in individual patients by defining so-called protein disease signatures (PDS). We feel that the integration of proteomics into the toolbox of pain researchers and physicians alike will open new avenues towards a better understanding and management of chronic pain. SIGNIFICANCE STATEMENT: The immense challenges associated with chronic pain call for urgent changes in pain research and management. Here, we highlight the enormous potential of a proteome-based systems biology approach for advancing our understanding of chronic pain from a mechanistic, translational and clinical angle.