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Affinity Proteomics Applied to Patient CSF Identifies Protein Profiles Associated with Neuropathic Pain and Fibromyalgia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden. (Affinity Proteomics)
SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden. (Affinity Proteomics)
SciLifeLab, School of Biotechnology, KTH – Royal Institute of Technology, Stockholm, Sweden. (Affinity Proteomics)
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: Today, there are no biological tests on which to base pain diagnoses, treatment choices or to understand the biological processes underlying and accompanying chronic pain for the individual pain patient. Relevant biological markers would greatly aid in diagnosis and treatment of patients with chronic pain. Our study aimed to find proteins in CSF associated with fibromyalgia and neuropathic pain, two common and poorly understood chronic pain conditions.

Methods: We have performed CSF protein profiling of 55 proteins using a 100-plex antibody suspension bead array. We collected, analyzed and compared CSF samples from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery and n=11 for verification), 40 patients with fibromyalgia and 135 controls without neurological disease from two different populations.

Results: We found significant differences in CSF protein levels between patients and controls (p<0.05). Among these proteins, Apolipoprotein C1 (APOC1) was found to be increased in CSF of neuropathic pain patients compared to controls and there was a non-significant trend for increased levels also in fibromyalgia patient CSF. Ectonucleotide pyrophosphatase (ENPP2, Autotaxin) was increased in the CSF of fibromyalgia patients compared to all other groups including neuropathic pain patients.  Multivariate analysis revealed partially overlapping and partially distinct CSF profiles in neuropathic pain patients compared with fibromyalgia and controls for several other proteins including angiotensinogen (AGT), prostaglandin-H2 D-isomerase (PTGDS), neurexin-1 (NRXN1), superoxide dismutase 1 (SOD1) and superoxide dismutase 3 (SOD3).

Conclusions: Our results, suggest that the CSF protein profiles of neuropathic pain and fibromyalgia patients may be different from each other and from those of controls. CSF levels of APOC1, ENPP2, AGT, PTGDS, NRXN1, SOD1 and SOD3 should be further investigated for their potential to serve as biomarkers of different kinds of pain pathophysiology.

Keyword [en]
cerebrospinal fluid, biomarker, human, chronic pain, neuropathic pain, fibromyalgia, spinal cord stimulation, mechanism of action, radiculopathy, protein, inflammation, neuroinflammation, mass spectrometry, antibody suspension bead array, protein profiling
National Category
Neurosciences Clinical Laboratory Medicine Health Sciences Anesthesiology and Intensive Care Biomedical Laboratory Science/Technology
Research subject
Anaesthesiology and Intensive Care; Bioinformatics; Biochemistry; Biology with specialization in Molecular Biology; Biomedical Laboratory Science; Chemistry with specialization in Analytical Chemistry; Clinical Chemistry; Medical Science; Molecular Medicine
Identifiers
URN: urn:nbn:se:uu:diva-326158OAI: oai:DiVA.org:uu-326158DiVA: diva2:1119183
Projects
Berzelii Technology Centre of Neurodiagnostics
Funder
AFA Insurance, 140341VINNOVASwedish Research Council
Available from: 2017-07-03 Created: 2017-07-03 Last updated: 2017-07-03
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