Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
Asta Arendt-Tranholm
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
James Turnbull
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK; Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division and NIHR Nottingham Biomedical Research Centre, School of Pharmacy, University of Nottingham, Nottingham, UK
Rakesh R. Jha
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK; Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division and NIHR Nottingham Biomedical Research Centre, School of Pharmacy, University of Nottingham, Nottingham, UK
David Onion
Flow Cytometry Facility, School of Life Sciences, University of Nottingham, Nottingham, UK
Tony Kelly
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
Afroditi Kouraki
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
Paul Millns
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
Sameer Gohir
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
Susan Franks
School of Mathematical Sciences, University of Nottingham, Nottingham, UK
David A. Barrett
Centre for Analytical Bioscience, Advanced Materials and Healthcare Technologies Division and NIHR Nottingham Biomedical Research Centre, School of Pharmacy, University of Nottingham, Nottingham, UK
Ana M. Valdes
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
Victoria Chapman
Pain Centre Versus Arthritis and NIHR Nottingham Biomedical Research Centre, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK; Corresponding author
Summary: Our goal was to probe the potential transcriptomic basis for the relationship between plasma levels of the specialized pro-resolving precursor, 17-hydroxy-docosahexaenoic acid (17-HDHA) and chronic pain. Participants with osteoarthritis (average age of 62.3, 60% were female, n = 30) were stratified by levels of 17-HDHA and self-reported pain scores. RNAs from CD14++/CD16-/CD66b-/HLA-DR+ (classical) monocytes were sequenced and differentially expressed mRNAs were identified with DESeq2. QIAGEN ingenuity pathway analysis identified the top ranked canonical biological pathway to be eukaryotic initiation factor 2 (EIF2) signaling (lower activation level in the low 17-HDHA-high pain group compared to the high 17-HDHA-low pain group (Z score −3)), followed by EIF4 and P70S6K signaling pathways and mTOR signaling. Our approach provides insight into the biological pathways contributing to the association between 17-HDHA and chronic osteoarthritis (OA) pain, identifying EIF2 signaling, with known roles in osteoclast differentiation, OA pathology, and pain, as a potential downstream target.
