巴氯芬缓减大鼠胫骨癌痛及可能机制

Baclofen attenuates pain in rat tibia bone cancer and its possible mechanism

目的探讨巴氯芬对大鼠胫骨癌痛的作用及可能机制。方法使用Walker256乳腺癌细胞建立SD大鼠胫骨癌痛模型,第9天64只模型大鼠随机分8组(n=8):N1、N2组(生理盐水10μl),B1、B2组(巴氯芬0.1μg),C1、C2组[γ-氨基丁酸B型受体(GABAB)特异性拮抗剂(CGP35348)60μg],D1、D2组(CGP3534860μg+巴氯芬0.1μg)。N1、B1、C1、D1组单次鞘内给药前0.5h、给药后0.5、1、2、4、8、24h使用VonFrey纤维测定患肢机械缩足阈值(MWT)。N2、B2、C2、D2组鞘内连续给药4d,每天给药1次,最后一次给药后6h处死,用免疫组织化学方法检测磷酸化细胞外信号调节激酶(p-ERK1/2)表达。结果与N1组比较,B1组大鼠MWT明显增加(P<0.05),持续时间为4h;与N2组比较,B2组大鼠脊髓背角p-ERK1/2阳性细胞数明显减少(P<0.05)。结论巴氯芬可能通过GABAB受体调控下游p-ERK1/2变化减缓胫骨癌痛,其作用可被CGP35348阻断。

Objective To study the analgesic effect of baclofen on rat tibia bone cancer pain and possible mechanism.Methods SD rat model with tibia bone cancer was established using Walker 256 breast carcinoma cells.On the 9th day,64 rats were randomly divided into 8 groups of N1,N2（NS 10 μl）,B1,B2（baclofen 0.1 μg）,C1,C2／[γ-aminobutyric acid B（GABAB） receptor antagonist（CGP35348） 60 μg／],D1,D2（CGP35348 60 μg plus baclofen 0.1 μg） with 8 rats each. Mechanical withdrawal threshold（MWT） of the affected limb in groups of N1,B1,C1 and D1 was record at 0.5 h before and 0.5,1,2,4,8 and 24 h after single intrathecal injection.The rats in groups of N2,B2,C2 and D2 were killed at 6 h after completion of drug injection（once a day for continuous 4 days） for phosphorylation extracellular signal-regulated kinase（p-ERK1/2） with immunohistochemical test.Results Compared to group N1,MWT was significantly increased in group B1（P0.05）,which lasted for 4 h.Compared to group N2,the positive p-ERK1/2 cells in spinal dorsal horn in group B2 were significantly decreased（P0.05）.Conclusion Baclofen may attenuate pain through GABAB receptor regulating the change of downstream p-ERK1/2 in rats model with tibia bone cancer pain,which can be blocked by CGP35348.