Abstract
Objectives: Although generalized muscle pain, tiredness, anxiety, and depression are commonly present among chronic widespread pain (CWP) patients, the molecular mechanisms behind CWP are not fully elucidated. Moreover, the lack of biomarkers often makes diagnosis and treatment problematic. In this study, we investigated the correlation between pain intensity, psychological distress, and plasma proteins among CWP patients and controls (CON).Methods: The plasma proteome of CWP (n = 15) and CON (n = 23) was analyzed using two-dimensional gel electrophoresis. Orthogonal Partial Least Square analysis (OPLS) was used to determine proteins associated with pain intensity (numeric rating scale) in CWP and psychological distress (Hospital and Depression Scale, HADS) in CWP and CON. Significant proteins were identified by MALDI-TOF and tandem MS.Results: In CWP, pain intensity was associated with plasma proteins mostly involved in metabolic and immunity processes (e.g., kininogen-1, fibrinogen gamma chain, and ceruloplasmin), and psychological distress was associated with plasma proteins related to immunity response, iron ion, and lipid metabolism (e.g., complement factor B, complement C1r subcomponent, hemopexin, and clusterin).Discussion: This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome. Using the plasma proteome profile of CWP to study potential biomarker candidates provides a snapshot of ongoing systemic mechanisms in CWP.
Highlights
Chronic widespread pain (CWP), including fibromyalgia syndrome (FMS), is a complex pain condition characterized by generalized musculoskeletal pain and is often associated with symptoms such as tiredness, sleep disturbance, depression, anxiety, and cognitive difficulties (Wolfe et al, 1990; Aparicio et al, 2013; Perez de Heredia-Torres et al, 2016)
Age Height Weight Body Mass Index (BMI) Pain duration numeric rating scale (NRS) Pain the last 7 days Neck (NRS) Shoulders (NRS) Low back (NRS) Hospital Anxiety and Depression Scale (HADS) depression HADS anxiety HADS total Pain Catastrophizing Scale (PCS) Quality of Life instrument (QoL) diagnosed with FM (n)
This study suggests that different plasma protein patterns are associated with different pain intensities and psychological distress in CWP
Summary
Chronic widespread pain (CWP), including fibromyalgia syndrome (FMS), is a complex pain condition characterized by generalized musculoskeletal pain and is often associated with symptoms such as tiredness, sleep disturbance, depression, anxiety, and cognitive difficulties (Wolfe et al, 1990; Aparicio et al, 2013; Perez de Heredia-Torres et al, 2016). The variety of symptoms among CWP and the complex multifactorial etiology make it difficult to study the biological mechanisms behind CWP, mechanisms that need further elucidation Both central and peripheral mechanisms may contribute to the perceived pain in CWP, (Staud et al, 2001, 2009; Flodin et al, 2014) no valid biological markers have been identified for the activated nociceptive mechanisms in chronic pain conditions, including CWP. 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). These studies clearly indicate that peripheral (muscle and/or blood) nociceptive and inflammatory mechanisms are active and differ between patients and healthy controls
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