Alterations of anti-inflammatory lipids in plasma from women with chronic widespread pain - a case control study

Abstract

Background: Chronic widespread pain conditions (CWP) such as the pain associated with fibromyalgia syndrome (FMS) are significant health problems with unclear aetiology. Although CWP and FMS can alter both central and peripheral pain mechanisms, there are no validated markers for such alterations. Pro- and anti-inflammatory components of the immune system such as cytokines and endogenous lipid mediators could serve as systemic markers of alterations in chronic pain. Lipid mediators associated with anti-inflammatory qualities - e.g., oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) - belong to N-acylethanolamines (NAEs). Previous studies have concluded that these lipid mediators may modulate pain and inflammation via the activation of peroxisome proliferator activating receptors (PPARs) and the activation of PPARs may regulate gene transcriptional factors that control the expression of distinct cytokines.

Methods: This study investigates NAEs and cytokines in 17 women with CWP and 21 healthy controls. Plasma levels of the anti-inflammatory lipids OEA, PEA, and SEA, the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 were investigated. T-test of independent samples was used for group comparisons. Bivariate correlation analyses, and multivariate regression analysis were performed between lipids, cytokines, and pain intensity of the participants.

Results: Significantly higher levels of OEA and PEA in plasma were found in CWP. No alterations in the levels of cytokines existed and no correlations between levels of lipids and cytokines were found.

Conclusions: We conclude that altered levels of OEA and PEA might indicate the presence of systemic inflammation in CWP. In addition, we believe our findings contribute to the understanding of the biochemical mechanisms involved in chronic musculoskeletal pain.

Keywords: Chronic widespread pain; Cytokines; Inflammation; N-acylethanolamines; Oleoylethanolamide; Palmitoylethanolamide.

Fig. 1

Scatter plots of concentrations (nM) in plasma for oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) sampled from women with chronic wide spread pain (CWP) and healthy female controls (CON). The horizontal lines illustrate the group mean (middle-line) with error bars (± SD) above and below

Fig. 2

Bivariate correlation for the three N-acyletanolamines in the two groups illustrated with scatterplots. Best fitted regression (R²) lines describe the direction of the correlation. In the CON (panel to the left), the directions are consistently positive. In the CWP (panel to the right), the direction is positive for PEA vs. SEA but weakly negative for OEA vs. PEA and OEA vs. SEA

Fig. 3

Variable importance of projection (VIP) values represented as bars with error bars of NAEs and cytokines. VIP > 1.0 is considered as significant. PEA, OEA, and SEA were the relatively strongest group-separating (CWP vs. CON) substances (VIP ≥ 1.30). The cytokines were relatively unimportant regressors in this context (VIP ≤ 0.86)