Systemic alterations in plasma proteins from women with chronic widespread pain compared to healthy controls: a proteomic study

Abstract

Chronic widespread pain (CWP) is a complex pain condition that is difficult to treat. The prevalence of CWP approximates ~10% of the general population, with higher prevalence in women. Lack of understanding of molecular mechanisms has been a challenge for diagnosis and treatment of chronic pain. The aim of this study was to explore the systemic protein changes in CWP compared to those in healthy controls (CON). By applying 2-dimensional gel electrophoresis, we analyzed the protein pattern of plasma samples from women with CWP (n=16) and healthy women (n=23). The proteomic data were analyzed using multivariate statistical models, and altered proteins were identified using mass spectrometry. The proteome analysis was further validated by gel-free Western blot. Multivariate statistical data analysis of quantified proteins revealed 22 altered proteins in women with CWP, compared to CON group. Many of the identified proteins are previously known to be involved in different parts of the complement system and metabolic and inflammatory processes, e.g., complement factor B, vitamin D-binding protein, ceruloplasmin, transthyretin and alpha-2-HS-glycoprotein. These results indicate that important systemic protein differences exist between women with CWP and healthy women. Further, this study illustrates the potential use of proteomics to detect biomarkers that may provide new insights into the molecular mechanism(s) of chronic pain. However, further larger investigations are required in order to confirm these findings before it will be possible to identify proteins as potential pain biomarkers for clinical use.

Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain

“…This resulted in 16 CWP and 23 CON samples. Hence, the proteomic data that this present study is based on has previously been published ( Wåhlén et al, 2017 ). However, in this present study, one of the CWP patients was excluded due to unclear diagnosis after detailed analysis and due to the fact that this patient had incomplete data in the health questionnaire.…”

“…To get a comprehensive description of the subjects also data from the Pain Catastrophizing Scale (PCS) and Quality of Life instrument (QoL) are reported; for details about these instruments see our previous studies ( Gerdle et al, 2014 ; Wåhlén et al, 2017 ).…”

“…This and other studies from our group focus on exploring such activated mechanisms with the long-term goal of identifying clinically applicable biomarkers that can facilitate mechanism-based diagnoses and choice of treatments. Many biomarker studies have analyzed protein patterns, cytokines/chemokines, lipids, and metabolites in plasma/serum, muscles, and saliva to understand activated nociceptive mechanisms in patients with CWP/FMS ( Bazzichi et al, 2009 ; Zanette et al, 2014 ; Hadrevi et al, 2015 ; Culic et al, 2016 ; Gerdle et al, 2017 ; Olausson et al, 2017 ; Wåhlén et al, 2017 ). Taken together, these studies clearly indicate that peripheral (muscle and/or blood) nociceptive and inflammatory mechanisms are active and differ between patients and healthy controls.…”

“…Previously, we used 2-DE to investigate the plasma proteome between CWP patients and healthy controls ( Wåhlén et al, 2017 ). We found several proteins belonging to inflammatory, immunity, and metabolic processes that could discriminate the CWP and CON group.…”

Proteomic profiling of proteins in the dorsal horn of the spinal cord in dairy cows with chronic lameness

“…Moreover, few proteomic studies have focused on naturally occurring pathological pain. Recently, the cerebrospinal fluid, serum and plasma proteome of human patients with neuropathic pain, rheumatoid arthritis and widespread back pain has been described [28,29,30].…”