Spinal SET SET 7/9 may contribute to the maintenance of cancer‐induced bone pain in mice

摘要

Summary Cancer‐induced bone pain ( CIBP ) profoundly influences patients' quality of life. Exploring the mechanisms by which CIBP occurs is essential for developing efficacious therapies. Various studies have shown that proinflammatory factors were involved in CIBP . SET domain containing lysine methyltransferase 7/9 ( SET 7/9) may modulate the expression of NF ‐κB‐dependent proinflammatory genes in vitro. However, whether SET 7/9 may participate in the maintenance of CIBP remains unknown. In this study, NCTC 2472 cells were inoculated into the intramedullary space of the femur to establish a mouse model of CIBP . Upregulation of spinal SET 7/9 expression was related to pain behaviours in tumour‐inoculated mice. Intrathecal cyproheptadine (10 or 20?nmol) attenuated response to painful stimuli in a dose‐dependent manner. Moreover, there was a concomitant decrease in spinal SET 7/9 and RANTES expression. The antinociceptive effects of cyproheptadine were abolished by pre‐intrathecal administration of SET 7/9 (0.2?μg) for 30?minutes before intrathecal cyproheptadine (20?nmol) administration. These results indicated that spinal SET 7/9 may contribute to the maintenance of CIBP in mice. Hence, targeting of spinal SET 7/9 might be a useful alternative therapy for the treatment of CIBP .