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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 investigate the effect and mechanism of baclofen on pain of tibia in rats. Methods Walker256 breast cancer cells were used to establish the model of tibial cancer pain in SD rats. On the 9th day, 64 rats were randomly divided into 8 groups (n = 8): N1 and N2 (normal saline 10μl), B1 and B2 (0.1 μg, 0.1 μg), group C1 and C2 [60 μg of GABAB specific antagonist (CGP35348)] and D1 and D2 groups (CGP3534860 μg and baclofen 0.1 μg). The N1, B1, C1 and D1 groups were measured 0.5 min before single intrathecal administration and 0.5, 1, 2, 4, 8, 24 h after the administration. Von Frey fibers were used to measure the mechanical contracting threshold (MWT) of limbs. The N2, B2, C2 and D2 groups were administered intrathecally for 4 days, once daily and 6 hours after the last administration. The expression of phosphorylated extracellular signal-regulated kinase (p-ERK1 / 2) was detected by immunohistochemistry . Results Compared with N1 group, the MWT of B1 group was significantly increased (P <0.05), and the duration was 4h. Compared with N2 group, the number of p-ERK1 / 2 positive cells in spinal dorsal horn of B2 group was significantly decreased (P <0.05 ). Conclusions Baclofen may reduce the pain of tibia by inhibiting the expression of p-ERK1 / 2 downstream of GABAB receptor, and its effect may be blocked by CGP35348.