• BjurströmMartin FloresMFDepartment of Anesthesiology and Intensive Care, Skåne University Hospital, Lund, Sweden.Department of Clinical Sciences Lund, Lund University, Lund, Sweden.Norman Cousins Center for Psychoneuroimmunology, Jane and Terry Semel Inst, Mikael Bodelsson, Agneta Montgomery, Andreas Harsten, Markus Waldén, Shorena Janelidze, Sara Hall, Oskar Hansson, Michael R Irwin, and Niklas Mattsson-Carlgren.
• Department of Anesthesiology and Intensive Care, Skåne University Hospital, Lund, Sweden.
• Pain. 2020 Sep 1; 161 (9): 2142-2154.

AbstractNeuroinflammation is implicated in the development and maintenance of persistent pain states, but there are limited data linking cerebrospinal fluid (CSF) inflammatory mediators with neurophysiological pain processes in humans. In a prospective observational study, CSF inflammatory mediators were compared between patients with osteoarthritis (OA) who were undergoing total hip arthroplasty due to disabling pain symptoms (n = 52) and pain-free comparison controls (n = 30). In OA patients only, detailed clinical examination and quantitative sensory testing were completed. Cerebrospinal fluid samples were analyzed for 10 proinflammatory mediators using Meso Scale Discovery platform. Compared to controls, OA patients had higher CSF levels of interleukin 8 (IL-8) (P = 0.002), intercellular adhesion molecule 1 (P = 0.007), and vascular cell adhesion molecule 1 (P = 0.006). Osteoarthritis patients with central sensitization possibly indicated by arm pressure pain detection threshold <250 kPa showed significantly higher CSF levels of Fms-related tyrosine kinase 1 (Flt-1) (P = 0.044) and interferon gamma-induced protein 10 (IP-10) (P = 0.024), as compared to subjects with PPDT above that threshold. In patients reporting pain numerical rating scale score ≥3/10 during peripheral venous cannulation, Flt-1 was elevated (P = 0.025), and in patients with punctate stimulus wind-up ratio ≥2, CSF monocyte chemoattractant protein 1 was higher (P = 0.011). Multiple logistic regression models showed that increased Flt-1 was associated with central sensitization, assessed by remote-site PPDT and peripheral venous cannulation pain, and monocyte chemoattractant protein-1 with temporal summation in the area of maximum pain. Multiple proinflammatory mediators measured in CSF are associated with persistent hip OA-related pain. Pain phenotype may be influenced by specific CSF neuroinflammatory profiles.Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.

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