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• W4254087504 abstract "Abstract Background: Chronic osteoarthritic pain is not well understood in terms of its pathophysiological mechanism. Activated glial cells are thought to play a role in the maintenance of chronic pain. T98G glioblastoma cell line was previously observed to release higher amounts of interleukin-6 (IL-6) when treated with cerebrospinal fluid (CSF) from patients with another chronic pain condition, post-herpetic neuralgia. In this study, we investigated the ability of CSF from patients diagnosed with knee osteoarthritis (OA) suffering from chronic pain, to trigger the release of pro-inflammatory cytokines, IL-6, IL-1beta and tumour necrosis factor alpha (TNF-α) from T98G. Characterization of upstream signalling was also explored. Methods: 15 OA patients undergoing total knee replacement and 15 patients without pain undergoing surgery with spinal anaesthesia were prospectively recruited. CSF was collected during anaesthesia prior to surgery. CSF were added to cultured T98G cells. IL-6, IL-1β and TNF-α release from T98G cells were measured using enzyme immunoassay. Antibody array and western blotting were performed on CSF-triggered T98G cell lysates to identify possible signalling targets. Age, gender and pain scores were recorded. Mann-Whitney U test was used to compare IL-6 release and protein expression between groups. Association between IL-6 and pain score was analysed using linear regression.Results: Compared to CSF of patients without pain, significantly higher IL-6 levels were released by T98G cells when induced by CSF from OA patients. The IL-6 levels showed positive association with pain score (adjusted B estimate= 10.1 (95% Confidence Interval 4.3-15.9); p= 0.001). Array conducted with OA pain patient pooled CSF identified several proteins being upregulated greater than 2-fold including STE20-related kinase adaptor protein and spleen tyrosine kinase. Further validation in western blotting of individual samples was unable to show similar significant increase.Conclusion: IL-6 is a potential biomarker crucial in the maintenance phase of chronic pain in both OA and post-herpetic neuralgia (PHN). Identification of signalling pathways involved in pain using pooled CSF on antibody array yield several protein of interest. However, those targets are inconsistent when individually validated using western blotting. Exploring other protein targets is required to identify the signalling mechanism of chronic pain." @default.
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• W4254087504 date "2019-10-08" @default.
• W4254087504 modified "2023-09-26" @default.
• W4254087504 title "Cerebrospinal fluid of chronic osteoarthritic patients induced interleukin-6 release in human glial cell-line T98G" @default.
• W4254087504 doi "https://doi.org/10.21203/rs.2.15747/v1" @default.
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