Abstract

Chronic widespread pain (CWP) is a complex pain condition characterized by generalized musculoskeletal pain and often associated with other symptoms. An important clinical feature is widespread increased pain sensitivity such as lowered pain thresholds for mechanical stimuli (pressure pain thresholds [PPT]). There is a growing interest in investigating the activated neurobiological mechanisms in CWP, which includes fibromyalgia. In CWP, strong significant correlations have been found between muscle protein patterns and PPT. This explorative proteomic study investigates the multivariate correlation pattern between plasma proteins and PPT in CWP and in healthy controls (CON). In addition, this study analyses whether the important proteins for PPT differ between the 2 groups.Using 2-dimensional gel electrophoresis, we analyzed the plasma proteome of the CWP (n = 15) and the CON (n = 23) and proteins were identified using mass spectrometry. For both the CWP and the CON, the associations between the identified proteins and PPT were analyzed using orthogonal partial least square in 2 steps.Significant associations between certain plasma proteins and PPT existed both in CWP (R = 0.95; P = .006) and in CON (R = 0.89; P < .001). For both groups of subjects, we found several proteins involved in PPT that reflect different biological processes. The plasma proteins as well as the biological processes involved in PPT differed markedly between the 2 groups of subjects.This study suggests that plasma protein patterns are associated with pain thresholds in CWP. Using the plasma proteome profile of CWP to study potential biomarker candidates could provide a snapshot of ongoing systemic mechanisms in CWP.

Highlights

  • Chronic widespread pain (CWP) is characterized by generalized musculoskeletal pain and often is associated with symptoms such as psychological distress, insomnia, fatigue, and cognitive difficulties.[1,2,3] CWP prevalence is 5% to 10%, with a higher prevalence in women.[4,5,6,7] Chronic pain, including CWP, affects patients and their families and society, leading to significant suffering and high socioeconomic burden.[7]CWP diagnosis is generally based on the first part of the criteria of the American College of Rheumatology (1990) definition for fibromyalgia (FM).[3]

  • This study suggests that plasma protein patterns are associated with pain thresholds in CWP

  • Clinical background data for the 2 groups have been presented elsewhere as mentioned above and are summarized in Table 1.[33] patients with CWP had significantly higher pain intensity, were significantly older, and reported significantly higher HADStotal compared to the CON (Table 1)

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Summary

Introduction

Chronic widespread pain (CWP) is characterized by generalized musculoskeletal pain and often is associated with symptoms such as psychological distress, insomnia, fatigue, and cognitive difficulties.[1,2,3] CWP prevalence is 5% to 10%, with a higher prevalence in women.[4,5,6,7] Chronic pain, including CWP, affects patients and their families and society, leading to significant suffering and high socioeconomic burden.[7]CWP diagnosis is generally based on the first part of the criteria of the American College of Rheumatology (1990) definition for fibromyalgia (FM).[3]. Peripheral and central mechanisms are believed to contribute to the clinical picture in CWP.[10,11,12]

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