Significant correlation between plasma proteome profile and pain intensity, sensitivity, and psychological distress in women with fibromyalgia

Abstract

Fibromyalgia (FM) is a complex pain condition where the pathophysiological and molecular mechanisms are not fully elucidated. The primary aim of this study was to investigate the plasma proteome profile in women with FM compared to controls. The secondary aim was to investigate if plasma protein patterns correlate with the clinical variables pain intensity, sensitivity, and psychological distress. Clinical variables/background data were retrieved through questionnaires. Pressure pain thresholds (PPT) were assessed using an algometer. The plasma proteome profile of FM (n = 30) and controls (n = 32) was analyzed using two-dimensional gel electrophoresis and mass spectrometry. Quantified proteins were analyzed regarding group differences, and correlations to clinical parameters in FM, using multivariate statistics. Clear significant differences between FM and controls were found in proteins involved in inflammatory, metabolic, and immunity processes. Pain intensity, PPT, and psychological distress in FM had associations with specific plasma proteins involved in blood coagulation, metabolic, inflammation and immunity processes. This study further confirms that systemic differences in protein expression exist in women with FM compared to controls and that altered levels of specific plasma proteins are associated with different clinical parameters.

Thermal Pain Thresholds Are Significantly Associated with Plasma Proteins of the Immune System in Chronic Widespread Pain—An Exploratory Pilot Study Using Multivariate and Network Analyses

“…We and others have reported marked significant differences both in blood and in muscle proteomes between CWP/FM and healthy controls [10,[23][24][25][26]. Moreover, both muscle and plasma protein patterns show strong significant correlations with pain intensity [25,27,28].…”

“…The strongest regression was obtained using proteomics. Recently, we reported that plasma proteins correlated with PPT in an FM cohort [25].…”

“…Compared to genome and transcriptome studies, investigating the proteome is more complex, including the choice of statistical methods [22]. We and others have reported marked significant differences both in blood and in muscle proteomes between CWP/FM and healthy controls [10,[23][24][25][26]. Moreover, both muscle and plasma protein patterns show strong significant correlations with pain intensity [25,27,28].…”

“…A broad sampling of plasma proteins was applied-i.e., proteins at nano and micro molar concentrations (proteomics) and at picomolar concentrations (cytokines, chemokines and growth factors)-to focus on protein interactions and possible biological processes. The latter approach was advocated before it will be possible to focus on key proteins [36,61] and is increasingly applied in proteomic blood and cerebrospinal fluid studies of CWP and FM [14,[23][24][25][26]62]. Plasma/serum proteome studies of CWP and FM cohorts have focussed on differentiating patients from controls, and low-grade peripheral inflammation appears to be involved in pathogenesis and maintenance of CWP and FM [10,17,[24][25][26]63].…”

“…The latter approach was advocated before it will be possible to focus on key proteins [36,61] and is increasingly applied in proteomic blood and cerebrospinal fluid studies of CWP and FM [14,[23][24][25][26]62]. Plasma/serum proteome studies of CWP and FM cohorts have focussed on differentiating patients from controls, and low-grade peripheral inflammation appears to be involved in pathogenesis and maintenance of CWP and FM [10,17,[24][25][26]63]. It is also important to examine the peripheral protein patterns in relation to clinical variables since it cannot be assumed that the same proteins responsible for group differentiation are important for clinical variables [36].…”