Effects of repeated injection of flurbiprofen axetil on bone cancer pain

Abstract

Objective To investigate the effects of repeated injection of flurbiprofen axetil on pain behaviors and side effects in a rat model of bone cancer pain.Methods 24 female SD rats were randomly divided into 3 groups(n=8) as follows.Sham group (S group): intra-tibial injection of 10 μl Hank's solution.Tumor group (T group): intra-tibial injection of 10 μl 4×105 Walker 256 mammary gland carcinoma cells.Flurbiprofen axetil group (Fa group): intraperitoneal injection of flurbiprofen axetil on day 15 to 21 after tumor model.Paw withdrawal mechanical threshold (PWMT) was tested on day 1 before surgery and days 1,3,5,7,10,14,15,17,19,21,24 after surgery.The blood,liver,kidney and ipsilateral tibial bone of all rats were obtained on day 24 to examine the pathological changes.Results ① Compared to S group,the PWMT in T group decreased significantly at day 5 after tumor surgery [(10.92±1.04) g vs (9.01±1.49) g,P＜0.05],and peaked at day 14 after surgery.Compared to T group,the PWMT in Fa group increased obviously at day 17[(6.64±1.70) g vs (4.06±1.69) g,P＜0.05].At day 21,the PWMT in Fa group was lower than that in S group [(8.04±0.81) g vs (10.31±1.35) g,P＜0.05].② The results of bleeding and clotting tests [prothrombin time(PT),activated partial prothrombin time (APTT),thrombin time (TT),fibrinogen (FIB),platelet (PLT)],hepatic and renal functional tests [glutamic-pyruvic transaminase (ALT),aspartate amino-transaminase (AST),total protein (TP),urea (UREA),creatinine (CREA)]had no significant difference among S group,T group and Fa group.③ HE staining revealed that there were no significant pathological changes in liver and renal tissue after repeated intraperitoneal injection of flurbiprofen axetil.Live tumor cells were found in tibia marrow cavities in both T and Fa groups.Conclusions Repeated intraperitoneal injection of flurbiprofen axetil could significantly attenuate bone cancer pain in rats while having no influence on hepatic and renal functions as well as hemostatic function. Key words: Flurbiprofen axetil; Bone cancer pain; Mechanical allodynia; Side effects