CSF levels of apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia

Anne-Li Lind,1 David Just,2 Maria Mikus,2 Claudia Fredolini,2 Marina Ioannou,2 Björn Gerdle,3 Bijar Ghafouri,3 Emmanuel Bäckryd,3 Lars Tanum,4 Torsten Gordh,1 Anna Månberg2 1Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; 2Division of Affinity Proteomics, SciLifeLab, Deptartment of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden; 3Pain and Rehabilitation Center, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; 4Department of R&D in Mental Health, Akershus University Hospital, Lørenskog, NorwayCorrespondence: Anna MånbergDivision of Affinity Proteomics, SciLifeLab, Department of Protein Science, KTH - Royal Institute of Technology, Tomtebodvägen 23A, Solna, Stockholm, SwedenTel +46 8 790 9803Email anna.manberg@scilifelab.seObjective: Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain.Methods: CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology.Results: We found increased levels of apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain.Conclusion: The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders.Keywords: cerebrospinal fluid, neuropathic pain, fibromyalgia, antibody suspension bead arrays, APOC1, ENPP2