Buprenorphine does not impact the inflammatory response in haemophilia A mice with experimentally-induced haemarthrosis

Haemarthrosis is the most common clinical manifestation of haemophilia and is responsible for significant morbidity in haemophilic patients. The murine experimentally-induced knee bleeding model is an important model in haemophilia research but it is currently unknown if the use of analgesia in this model might impact on the inflammatory response. The aim was to investigate the inflammatory response after a needle induced knee bleed in haemophilia A mice treated with buprenorphine or saline. One hundred and sixty mice were randomized into two groups to blindly receive buprenorphine or saline. All the mice were anaesthetized and knee injury was induced by inserting a 30 G needle into the right knee joint. At t = 6, 24, 48 and 72 h, 20 mice from each group were terminated and the following parameters were assessed: change in body weight and joint diameter, visual bleeding score (VBS), white blood counts, haematocrit, platelet concentrations, haemoglobin, plasma haptoglobin and plasma and synovial fluid levels of 23 cytokines. Twenty mice were terminated at t = 0 receiving no injury or treatment to provide baseline measures. Twenty-one cytokines in plasma and 22 cytokines in synovial fluid, joint diameter change, VBS and blood parameters were not significantly altered by the administration of buprenorphine. Slight alterations of plasma haptoglobin at t = 48 h, body weight, plasma and synovial eotaxin and plasma G-CSF were found in buprenorphine-treated mice. We demonstrated that buprenorphine does not overall impact on the inflammatory response, and the use of buprenorphine in the knee bleeding model in haemophilic mice should be continued.