Chronic widespread pain (CWP), including fibromyalgia (FM), is a complex pain condition, where little is known about the molecular mechanisms contributing to its pathophysiology. To date, there are no established biomarkers for CWP/FM. This thesis has investigated potential molecular mechanisms and biomarkers in blood for chronic pain in women with CWP/FM. Furthermore, investigations are made to evaluate whether common pain characteristics such as pain intensity, sensitivity, and psychological distress in CWP/FM are correlated with specific proteins in blood. The pain profile of CWP/FM, which includes the plasma proteome and clinical characteristics, is analyzed using proteomics, advanced multivariate statistics, and bioinformatics. The results from paper I, III, and IV indicate that there are prominent systemic changes related to immunity, inflammation, and metabolic processes in women with CWP/FM compared to healthy controls. Furthermore, STRING Search tool for retrieval of interacting genes/proteins VAS Visual Analogue Scale VIP Variable influence on projection Biopsychosocial model As all individuals are unique, the experience of pain is unique. Pain is described in biological terms as central and peripheral sensitization as well as influenced by numerous factors that could be explained to some extent by the concepts of the biopsychosocial model. This model considers the biological, psychological and social factors that can influence pain [46]. Biological factors such as diseases severity, nociception, inflammation, genetics, and brain function, could all be possible biomarkers. Examples of psychological factors are catastrophizing thoughts, anxiety/depression, coping, and stress. Social factors include Shotgun proteomics The principle of LC-MS/MS based proteomics is described below. The digested sample containing a complex mix of peptides, is initially separated on a column by a reversed-phase high pressure liquid chromatography (HPLC) system. The column can be of various length, diameters, and packed materials (e.g., C18 and silica). The peptides entering the column will bind according to their hydrophobicity and will further be eluted by an increasing concentration of 1990