Clear differences in cerebrospinal fluid proteome between women with chronic widespread pain and healthy women – a multivariate explorative cross-sectional study

Abstract

Introduction

Frequent chronic local pain can develop into chronic widespread pain (CWP). The spread of pain is correlated with pain intensity, anxiety, and depression, conditions that ultimately lead to a poor quality of life. Knowledge is incomplete about CWP’s etiology, although it has been suggested that both central hyperexcitability and/or a combination with peripheral factors may be involved. Cerebrospinal fluid (CSF) could act as a mirror for the central nervous system as proteins are signal substances that activate the formation of algesics and control nociceptive processes. To this end, this study investigates the CSF protein expression in women with CWP and in female healthy controls.

Materials and methods

This study included 12 female patients with CWP diagnosed according to the American College of Rheumatology criteria with 13 healthy age- and sex-matched pain-free subjects. All subjects went through a clinical examination and answered a health questionnaire that registered sociodemographic and anthropometric data, pain characteristics, psychological status, and quality of life rating. CSF was collected by lumbar puncture from each subject. Two-dimensional gel electrophoresis in combination with mass spectrometry was used to analyze the CSF proteome. This study identifies proteins that significantly discriminate between the two groups using multivariate data analysis (MVDA) (i.e., orthogonal partial least squares discriminant analysis [OPLS-DA]).

Results

There were no clinically significant levels of psychological distress and catastrophization presented in subjects with CWP. MVDA revealed a highly significant OPLS-DA model where 48 proteins from CSF explained 91% (R²) of the variation and with a prediction of 90% (Q²). The highest discriminating proteins were metabolic, transport, stress, and inflammatory.

Conclusion

The highest discriminating proteins (11 proteins), according to the literature, are involved in apoptotic regulations, anti-inflammatory and anti-oxidative processes, the immune system, and endogenous repair. The results of this explorative study may indicate the presence of neuro-inflammation in the central nervous system of CWP patients. Future studies should be larger and control for confounders and determine which alterations are unspecific/general and which are specific changes.

Keywords:

• biomarkers
• muscle pain
• inflammation

Supplementary material

Table S1 Altered proteins in cerebrospinal fluid identified by 2-DE and nLC-MS/MS.

Acknowledgments

We gratefully appreciate the people who donated CSF for this study, and we would like to thank nurses Marie Berggården, Anna Peterson, and Eva-Britt Lindh for their valuable help with the sample collection. This study was supported by the Swedish Research Council (K2015-99x-21874-05-4), Medical Research Council of Southeast Sweden (FORSS-159031), Region Östergötland (LIO-35923, SC-2013-00395-36), and AFA Insurance (140341). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.